• Principal Investigator
  • Male

Prof. dr. H. Spits

Position: Professor
Main activities: Research
Specialisation: Immunology
foto H. Spits is one of the AMC Principal Investigators
Focus of research:

The research focuses on understanding the biology of innate lymphoid cells which are important regulators and effectors of tissue immunity, homeostasis remodeling and repair. A second program is directed at optimising development of human immune system mice and a third to generate fully human monoclonal antibodies against tumor antigens 

 

AMC themes: Infection & Immunity, Metabolic disorders and gastrointestinal diseases
Departments: Experimental Immunology
Bernink JH, Mjösberg J , Spits H, Human ILC1: To Be or Not to Be. IMMUNITY 2017;46 (5):756-757 [PubMed]
Bruins JJ, Westphal AH, Albada B, Wagner K, Bartels L, Spits H, van Berkel WJH, van Delft FL, Inducible, Site-Specific Protein Labeling by Tyrosine Oxidation-Strain-Promoted (4+2) Cycloaddition. BIOCONJUGATE CHEM 2017;28 (4):1189-1193 [PubMed]
Gillissen MA, de Jong G, Kedde M, Yasuda E, Levie SE, Moiset G, Hensbergen PJ, Bakker AQ, Wagner K, Villaudy J, van Helden PM, Spits H, Hazenberg MD, Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice. BLOOD ADV 2017;1 (19):1551-1564
Gillissen MA, Kedde M, de Jong G, Moiset G, Yasuda E, Levie SE, Bakker AQ, Claassen YB, Wagner K, Böhne M, Hensbergen PJ, Speijer D, van Helden PM, Beaumont T, Spits H, Hazenberg MD, AML-specific cytotoxic antibodies in patients with durable graft versus leukemia responses. BLOOD 2017;ahead of print [PubMed]
Levels MJ, van Tok MN, Cantaert T, Cañete JD, Kroese FGM, Germar K, Spits H, Baeten DLP , Yeremenko NG, The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation. ARTHRITIS RHEUMATOL 2017;69 (4):750-762 [PubMed]
Merat SJ, van de Berg D, Bru C, Yasuda E, Breij E, Koostra N, Prins M, Molenkamp R, Bakker AQ, de Jong MD, Spits H, Schinkel J, Beaumont T, Multiplex flow cytometry-based assay to study the breadth of antibody responses against E1E2 glycoproteins of hepatitis C virus. J IMMUNOL METHODS 2017;ahead of print [PubMed]
Nagasawa M, Germar K, Blom B, Spits H, Human CD5(+) Innate Lymphoid Cells Are Functionally Immature and Their Development from CD34(+) Progenitor Cells Is Regulated by Id2. FRONT IMMUNOL 2017;8:1047 [PubMed]
Shikhagaie MM, Björklund ÅK, Mjösberg J , Erjefält JS, Cornelissen AS, Ros XR, Bal SM, Koning JJ, Mebius RE, Mori M, Bruchard M, Blom B, Spits H, Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates. CELL REP 2017;18 (7):1761-1773 [PubMed]
Shikhagaie MM, Germar K, Bal SM, Ros XR, Spits H, Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases. NAT REV RHEUMATOL 2017;13 (3):164-173 [PubMed]
Bal SM, Bernink JH, Nagasawa M, Groot J, Shikhagaie MM, Golebski K , van Drunen CM, Lutter R, Jonkers RE, Hombrink P, Bruchard M, Villaudy J, Munneke JM, Fokkens W, Erjefält JS, Spits H, Ros XR, IL-1β, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs. NAT IMMUNOL 2016;17 (6):636-645 [PubMed]
Bernink JH. The biology of human innate lymphoid cells. S.l.: s.n.; 2016. 173p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Bernink JH, Spits H, de Jonge WJ, A new edge to immune surveillance by the neural system. CELL RES 2016;26 (11):1178-1179 [PubMed]
Gillissen MA, de Jong G, Levie SE, Yasuda E, Bakker AQ, Evers LM, Pals ST, Huisman C, van Helden PM, Spits H, Hazenberg MD, AML relapse after rituximab treatment for GvHD: crucial role for B cells in GvL responses. BONE MARROW TRANSPL 2016;51 (9):1245-1248 [PubMed]
Gillissen MA, Yasuda E, de Jong G, Levie SE, Go D, Spits H, van Helden PM, Hazenberg MD, The modified FACS calcein AM retention assay: A high throughput flow cytometer based method to measure cytotoxicity. J IMMUNOL METHODS 2016;434:16-23 [PubMed]
Kerkman PF, Fabre E, van der Voort EIH, Zaldumbide A, Rombouts Y, Rispens T, Wolbink G, Hoeben RC, Spits H, Baeten DLP , Huizinga TWJ, Toes REM, Scherer HU, Identification and characterisation of citrullinated antigen-specific B cells in peripheral blood of patients with rheumatoid arthritis. ANN RHEUM DIS 2016;75 (6):1170-1176 [PubMed]
Kwakkenbos MJ, Diehl SA, Yasuda E, Bakker AQ, van Geelen CMM, Lukens MV, van Bleek GM, Widjojoatmodjo MN, Bogers WMJM, Mei H, Radbruch A, Scheeren FA, Spits H, Beaumont T, Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming (vol 16, pg 123, 2010). NAT MED 2016;22 (12):1502 [PubMed]
Kwakkenbos MJ, van Helden PM, Beaumont T, Spits H, Stable long-term cultures of self-renewing B cells and their applications. IMMUNOL REV 2016;270 (1):65-77 [PubMed]
Linnemann C, van Buuren MM, Bies L, Verdegaal EME, Schotte R, Calis JJA, Behjati S, Velds A, Hilkmann H, El Atmioui D, Visser M, Stratton MR, Haanen JBAG, Spits H, van der Burg SH, Schumacher TNM, High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4(+) T cells in human melanoma (vol 21, pg 81, 2015). NAT MED 2016;22 (10):1192 [PubMed]
Li Y, Mention JJ, Court N, Masse-Ranson G, Toubert A, Spits H, Legrand N, Corcuff E, Strick-Marchand H, Di Santo JP, A novel Flt3-deficient HIS mouse model with selective enhancement of human DC development. EUR J IMMUNOL 2016;46 (5):1291-1299 [PubMed]
Merat SJ, Molenkamp R, Wagner K, Koekkoek SM, van de Berg D, Yasuda E, Böhne M, Claassen YB, Grady BP, Prins M, Bakker AQ, de Jong MD, Spits H, Schinkel J, Beaumont T, Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance. PLOS ONE 2016;11 (10):e0165047 [PubMed]
Mjösberg J , Spits H, Human innate lymphoid cells. J ALLERGY CLIN IMMUN 2016;138 (5):1265-1276 [PubMed]
Munneke JM. Innate lymphoid cells in inflammation and repair. S.l.: s.n.; 2016. 184p. ISBN 978-94-028-0188-0 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, van Oers MHJ; copromotor(s): Hazenberg MD)
Peters CP, Mjösberg JM, Bernink JH, Spits H, Innate lymphoid cells in inflammatory bowel diseases. IMMUNOL LETT 2016;172:124-131 [PubMed]
Spits H, Bernink JH, Lanier L, NK cells and type 1 innate lymphoid cells: partners in host defense. NAT IMMUNOL 2016;17 (7):758-764 [PubMed]
Vély F, Barlogis V, Vallentin B, Neven B, Piperoglou C, Ebbo M, Perchet T, Petit M, Yessaad N, Touzot F, Bruneau J, Mahlaoui N, Zucchini N, Farnarier C, Michel G, Moshous D, Blanche S, Dujardin A, Spits H, Distler JHW, Ramming A, Picard C, Golub R, Fischer A, Vivier E, Evidence of innate lymphoid cell redundancy in humans. NAT IMMUNOL 2016;17 (11):1291-1299 [PubMed]
Vély F, Barlogis V, Vallentin B, Neven B, Piperoglou C, Perchet T, Petit M, Yessaad N, Touzot F, Bruneau J, Mahlaoui N, Zucchini N, Farnarier C, Michel G, Moshous D, Blanche S, Dujardin A, Spits H, Distler JHW, Ramming A, Picard C, Golub R, Fischer A, Vivier E, Corrigendum: Evidence of innate lymphoid cell redundancy in humans. NAT IMMUNOL 2016;17 (12):1479 [PubMed]
Verdegaal EME, de Miranda NFCC, Visser M, Harryvan T, van Buuren MM, Andersen RS, Hadrup SR, van der Minne CE, Schotte R, Spits H, Haanen JBAG, Kapiteijn EHW, Schumacher TN, van der Burg SH, Neoantigen landscape dynamics during human melanoma-T cell interactions. NATURE 2016;536 (7614):91-+ [PubMed]
Artis D, Spits H, The biology of innate lymphoid cells. NATURE 2015;517 (7534):293-301 [PubMed]
Bernink JH, Krabbendam L, Germar K, de Jong E, Gronke K, Kofoed-Nielsen M, Munneke JM, Hazenberg MD, Villaudy J, Buskens CJ, Bemelman WA, Diefenbach A, Blom B, Spits H, Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria. IMMUNITY 2015;43 (1):146-160 [PubMed]
Calpe S, Wagner K, El Khattabi M, Rutten L, Zimberlin C, Dolk E, Verrips CT, Medema JP, Spits H, Krishnadath KK, Effective Inhibition of Bone Morphogenetic Protein Function by Highly Specific Llama-Derived Antibodies. MOL CANCER THER 2015;14 (11):2527-2540 [PubMed]
Jachimowski LCM. Regulation of the multifaceted functions of human plasmacytoid dendritic cells: a polyphonic policy. S.l.: s.n.; 2015. 184p. ISBN 978-94-6182-538-4 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Uittenbogaart CH; copromotor(s): Blom B)
Linnemann C, van Buuren MM, Bies L, Verdegaal EME, Schotte R, Calis JJA, Behjati S, Velds A, Hilkmann H, Atmioui DE, Visser M, Stratton MR, Haanen JBAG, Spits H, van der Burg SH, Schumacher TNM, High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4(+) T cells in human melanoma. NAT MED 2015;21 (1):81-85 [PubMed]
Rosilio C, Nebout M, Imbert V, Griessinger E, Neffati Z, Benadiba J, Hagenbeek T, Spits H, Reverso J, Ambrosetti D, Michiels JF, Bailly-Maitre B, Endou H, Wempe MF, Peyron JF, L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia. LEUKEMIA 2015;29 (6):1253-1266 [PubMed]
Spits H, TOX sets the stage for innate lymphoid cells. NAT IMMUNOL 2015;16 (6):594-595 [PubMed]
Strick-Marchand H, Dusséaux M, Darche S, Huntington ND, Legrand N, Masse-Ranson G, Corcuff E, Ahodantin J, Weijer K, Spits H, Kremsdorf D, Di Santo JP, A novel mouse model for stable engraftment of a human immune system and human hepatocytes. PLOS ONE 2015;10 (3):e0119820 [PubMed]
Bernink JH, Germar K, Spits H, The role of ILC2 in pathology of type 2 inflammatory diseases. CURR OPIN IMMUNOL 2014;31:115-120 [PubMed]
Friesen RHE, Lee PS, Stoop EJM, Hoffman RMB, Ekiert DC, Bhabha G, Yu W, Juraszek J, Koudstaal W, Jongeneelen M, Korse HJWM, Ophorst C, Brinkman-van der Linden ECM, Throsby M, Kwakkenbos MJ, Bakker AQ, Beaumont T, Spits H, Kwaks T, Vogels R, Ward AB, Goudsmit J, Wilson IA, A common solution to group 2 influenza virus neutralization. P NATL ACAD SCI USA 2014;111 (1):445-450 [PubMed]
Hagenbeek TJ, Wu X, Choy L, Sanchez-Irizarry C, Seshagiri S, Stinson J, Siebel CW, Spits H, Murine Pten(-/-) T-ALL requires non-redundant PI3K/mTOR and DLL4/Notch1 signals for maintenance and γc/TCR signals for thymic exit. CANCER LETT 2014;346 (2):237-248 [PubMed]
Hazenberg MD, Spits H, Human innate lymphoid cells. BLOOD 2014;124 (5):700-709 [PubMed]
Kwakkenbos MJ, Bakker AQ, van Helden PM, Wagner K, Yasuda E, Spits H, Beaumont T, Genetic manipulation of B cells for the isolation of rare therapeutic antibodies from the human repertoire. METHODS 2014;65 (1):38-43 [PubMed]
McKenzie ANJ, Spits H, Eberl G, Innate lymphoid cells in inflammation and immunity. IMMUNITY 2014;41 (3):366-374 [PubMed]
Munneke JM, Björklund AT, Mjösberg JM, Garming-Legert K, Bernink JH, Blom B, Huisman C, van Oers MHJ, Spits H, Malmberg KJ, Hazenberg MD, Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. BLOOD 2014;124 (5):812-821 [PubMed]
Peters CP. Crohn's disease: mucosal immunology and immune modulating therapy. s.l.: s.n.; 2014. 187p. ISBN 9789462590625 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Fockens P; copromotor(s): te Velde AA, Ponsioen CY)
Spits H, New models of human immunity. NAT BIOTECHNOL 2014;32 (4):335-336 [PubMed]
Teunissen MBM, Munneke JM, Bernink JH, Spuls PI, Res PCM, te Velde A, Cheuk S, Brouwer MWD, Menting SP, Eidsmo L, Spits H, Hazenberg MD, Mjösberg J, Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients. J INVEST DERMATOL 2014;134 (9):2351-2360 [PubMed]
Villaudy J, Schotte R, Legrand N, Spits H, Critical assessment of human antibody generation in humanized mouse models. J IMMUNOL METHODS 2014;410:18-27 [PubMed]
Wagner K, Kwakkenbos MJ, Claassen YB, Maijoor K, Böhne M, van der Sluijs KF, Witte MD, van Zoelen DJ, Cornelissen LA, Beaumont T, Bakker AQ, Ploegh HL, Spits H, Bispecific antibody generated with sortase and click chemistry has broad antiinfluenza virus activity. P NATL ACAD SCI USA 2014;111 (47):16820-16825 [PubMed]
Xue L, Salimi M, Panse I, Mjösberg JM, McKenzie ANJ, Spits H, Klenerman P, Ogg G, Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J ALLERGY CLIN IMMUN 2014;133 (4):1184-1194 [PubMed]
Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjösberg JM, Spits H, Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. NAT IMMUNOL 2013;14 (3):221-229 [PubMed]
Bernink J, Mjösberg J , Spits H, Th1- and Th2-like subsets of innate lymphoid cells. IMMUNOL REV 2013;252 (1):133-138 [PubMed]
Centlivre M, Legrand N, Klamer S, Liu YP, Eije KJv, Bohne M, Rijnstra ESv, Weijer K, Blom B, Voermans C, Spits H, Berkhout B, Preclinical In Vivo Evaluation of the Safety of a Multi-shRNA-based Gene Therapy Against HIV-1. MOL THER-NUCL ACIDS 2013;2:e120 [PubMed]
Gentek R. Mechanisms of Notch signaling specifity in lymphocytes and their leukemic counterparts. s.l.: s.n.; 2013. 230p. ISBN 9789461823908 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Amsen D)
Gentek R, Munneke JM, Helbig C, Blom B, Hazenberg MD, Spits H, Amsen D, Modulation of signal strength switches Notch from an inducer of T cells to an inducer of ILC2. FRONT IMMUNOL 2013;4:UNSP 334 [PubMed]
Hazenbos WLW, Kajihara KK, Vandlen R, Morisaki JH, Lehar SM, Kwakkenbos MJ, Beaumont T, Bakker AQ, Phung Q, Swem LR, Ramakrishnan S, Kim J, Xu M, Shah IM, Diep BA, Sai T, Sebrell A, Khalfin Y, Oh A, Koth C, Lin SJ, Lee BC, Strandh M, Koefoed K, Andersen PS, Spits H, Brown EJ, Tan MW, Mariathasan S, Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins. PLOS PATHOG 2013;9 (10):e1003653 [PubMed]
Karrich JJ. Plasmacytoid dendritic cells: how to control the good, the bad, the ugly at the molecular level. s.l.: s.n.; 2013. 192p. ISBN 9789461822314 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Kopf M, Spits H, Lymphocyte development. CURR OPIN IMMUNOL 2013;25 (2):127-129 [PubMed]
Linnemann C, Heemskerk B, Kvistborg P, Kluin RJC, Bolotin DA, Chen X, Bresser K, Nieuwland M, Schotte R, Michels S, Gomez-Eerland R, Jahn L, Hombrink P, Legrand N, Shu CJ, Mamedov IZ, Velds A, Blank CU, Haanen JBAG, Turchaninova MA, Kerkhoven RM, Spits H, Hadrup SR, Heemskerk MHM, Blankenstein T, Chudakov DM, Bendle GM, Schumacher TNM, High-throughput identification of antigen-specific TCRs by TCR gene capture. NAT MED 2013;19 (11):1534-1541 [PubMed]
Lounnas N, Rosilio C, Nebout M, Mary D, Griessinger E, Neffati Z, Chiche J, Spits H, Hagenbeek TJ, Asnafi V, Poulsen SA, Supuran CT, Peyron JF, Imbert V, Pharmacological inhibition of carbonic anhydrase XII interferes with cell proliferation and induces cell apoptosis in T-cell lymphomas. CANCER LETT 2013;333 (1):76-88 [PubMed]
McLellan JS, Chen M, Joyce MG, Sastry M, Stewart-Jones GBE, Yang Y, Zhang B, Chen L, Srivatsan S, Zheng A, Zhou T, Graepel KW, Kumar A, Moin S, Boyington JC, Chuang GY, Soto C, Baxa U, Bakker AQ, Spits H, Beaumont T, Zheng Z, Xia N, Ko SY, Todd JP, Rao S, Graham BS, Kwong PD, Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus. SCIENCE 2013;342 (6158):592-598 [PubMed]
Rosilio C, Lounnas N, Nebout M, Imbert V, Hagenbeek T, Spits H, Asnafi V, Pontier-Bres R, Reverso J, Michiels JF, Sahra IB, Bost F, Peyron JF, The metabolic perturbators metformin, phenformin and AICAR interfere with the growth and survival of murine PTEN-deficient T cell lymphomas and human T-ALL/T-LL cancer cells. CANCER LETT 2013;336 (1):114-126 [PubMed]
Sonnenberg GF, Mjösberg J , Spits H, Artis D, SnapShot: innate lymphoid cells. IMMUNITY 2013;39 (3):622-622.e1 [PubMed]
Spits H, Group 2 innate lymphoid cells show up in the skin. IMMUNOL CELL BIOL 2013;91 (6):390-392 [PubMed]
Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Vivier E, Innate lymphoid cells--a proposal for uniform nomenclature. NAT REV IMMUNOL 2013;13 (2):145-149 [PubMed]
Diehl SA, Schmidlin H, Nagasawa M, Blom B, Spits H, IL-6 Triggers IL-21 production by human CD4(+) T cells to drive STAT3-dependent plasma cell differentiation in B cells. IMMUNOL CELL BIOL 2012;90 (8):802-811 [PubMed]
Hoorweg K, Peters CP, Cornelissen F, Aparicio-Domingo P, Papazian N, Kazemier G, Mjösberg JM, Spits H, Cupedo T, Functional differences between human NKp44(-) and NKp44(+) RORC+ innate lymphoid cells. FRONT IMMUNOL 2012;3:72 [PubMed]
Mjösberg J , Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, te Velde AA, Fokkens WJ, van Drunen CM, Spits H, The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. IMMUNITY 2012;37 (4):649-659 [PubMed]
Mjösberg J , Bernink J, Peters C, Spits H, Transcriptional control of innate lymphoid cells. EUR J IMMUNOL 2012;42 (8):1916-1923 [PubMed]
Mjösberg J , Spits H, Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation. EUR J IMMUNOL 2012;42 (5):1093-1096 [PubMed]
Spits H, Cupedo T, Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function. ANNU REV IMMUNOL 2012;30:647-675 [PubMed]
Spits H, Mjösberg J, The Aryl Hydrocarbon Receptor: A Sentinel Safeguarding the Survival of Immune Cells in the Gut. IMMUNITY 2012;36 (1):5-7 [PubMed]
Weder P, Schumacher TNM, Spits H, Luiten RM, Testing for HLA/peptide tetramer-binding to the T cell receptor complex on human T lymphocytes.. RESULTS IMMUNOL 2012;17:88-96
Elzinga G, van Doorn J, Wiersema AM, Klicks RJ, Andriessen A, Alblas JG, Spits H, Post A, van Gent M, Clinical evaluation of a PHMB-impregnated biocellulose dressing on paediatric lacerations. J WOUND CARE 2011;20 (6):280-284 [PubMed]
Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Mention JJ, Plet A, Weijer K, Jacques Y, Becker PD, Guzman C, Soussan P, Kremsdorf D, Spits H, Di Santo JP, IL-15 transpresentation promotes both human T-cell reconstitution and T-cell-dependent antibody responses in vivo. P NATL ACAD SCI USA 2011;108 (15):6217-6222 [PubMed]
Huntington ND, Alves NL, Legrand N, Lim A, Strick-Marchand H, Plet A, Weijer K, Jacques Y, Spits H, Di Santo JP, Autonomous and extrinsic regulation of thymopoiesis in human immune system (HIS) mice. EUR J IMMUNOL 2011;41 (10):2883-2893 [PubMed]
Legrand N, Huntington ND, Nagasawa M, Bakker AQ, Schotte R, Strick-Marchand H, de Geus SJ, Pouw SM, Böhne M, Voordouw A, Weijer K, Di Santo JP, Spits H, Functional CD47/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo. P NATL ACAD SCI USA 2011;108 (32):13224-13229 [PubMed]
Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H, Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. NAT IMMUNOL 2011;12 (11):1055-1062 [PubMed]
O'Garra A, Gabryšová L, Spits H, Quantitative events determine the differentiation and function of helper T cells. NAT IMMUNOL 2011;12 (4):288-294 [PubMed]
Pidasheva S, Trifari S, Phillips A, Hackney JA, Ma Y, Smith A, Sohn SJ, Spits H, Little RD, Behrens TW, Honigberg L, Ghilardi N, Clark HF, Functional studies on the IBD susceptibility gene IL23R implicate reduced receptor function in the protective genetic variant R381Q. PLOS ONE 2011;6 (10):e25038 [PubMed]
Scheeren FA, van Geelen CMM, Yasuda E, Spits H, Beaumont T, Antigen-Specific Monoclonal Antibodies Isolated from B Cells Expressing Constitutively Active STAT5. PLOS ONE 2011;6 (4):e17189 [PubMed]
Spits H, Another Armament in Gut Immunity: Lymphotoxin-Mediated Crosstalk between Innate Lymphoid and Dendritic Cells. CELL HOST MICROBE 2011;10 (1):3-4 [PubMed]
Spits H, Di Santo JP, The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. NAT IMMUNOL 2011;12 (1):21-27 [PubMed]
Wils EJ, Rombouts EJC, van Mourik I, Spits H, Legrand N, Braakman E, Cornelissen JJ, Stem cell factor consistently improves thymopoiesis after experimental transplantation of murine or human hematopoietic stem cells in immunodeficient mice. J IMMUNOL 2011;187 (6):2974-2981 [PubMed]
Becker PD, Legrand N, van Geelen CMM, Noerder M, Huntington ND, Lim A, Yasuda E, Diehl SA, Scheeren FA, Ott M, Weijer K, Wedemeyer H, Di Santo JP, Beaumont T, Guzman CA, Spits H, Generation of human antigen-specific monoclonal IgM antibodies using vaccinated "human immune system" mice. PLOS ONE 2010;5 (10):e13137 [PubMed]
Crellin NK, Trifari S, Kaplan CD, Cupedo T, Spits H, Human NKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineage distinct from conventional natural killer cells. J EXP MED 2010;207 (2):281-290 [PubMed]
Crellin NK, Trifari S, Kaplan CD, Satoh-Takayama N, Di Santo JP, Spits H, Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2. IMMUNITY 2010;33 (5):752-764 [PubMed]
Kis LL, Salamon D, Persson EK, Nagy N, Scheeren FA, Spits H, Klein G, Klein E, IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter. P NATL ACAD SCI USA 2010;107 (2):872-877 [PubMed]
Kwakkenbos MJ, Diehl SA, Yasuda E, Bakker AQ, van Geelen CMM, Lukens MV, van Bleek GM, Widjojoatmodjo MN, Bogers WMJM, Mei H, Radbruch A, Scheeren FA, Spits H, Beaumont T, Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. NAT MED 2010;16 (1):123-U164 [PubMed]
Scheeren FA, van Lent AU, Nagasawa M, Weijer K, Spits H, Legrand N, Blom B, Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation. EUR J IMMUNOL 2010;40 (4):955-965 [PubMed]
Schotte R, Dontje W, Nagasawa M, Yasuda Y, Bakker AQ, Spits H, Blom B, Synergy between IL-15 and Id2 Promotes the Expansion of Human NK Progenitor Cells, Which Can Be Counteracted by the E Protein HEB Required To Drive T Cell Development. J IMMUNOL 2010;184 (12):6670-6679 [PubMed]
Schotte R, Schmidlin H, Nagasawa M, Dontje W, Karrich JJ, Uittenbogaart C, Spits H, Blom B, Isolation and in vitro generation of gene-manipulated human plasmacytoid and conventional dendritic cells. METHODS MOL BIOL 2010;595:67-85 [PubMed]
Trifari S, Spits H, IL-22-producing CD4(+) T cells: Middle-men between the immune system and its environment. EUR J IMMUNOL 2010;40 (9):2369-2371 [PubMed]
van Lent AU, Centlivre M, Nagasawa M, Karrich JJ, Pouw SM, Weijer K, Spits H, Blom B, Legrand N, In vivo modulation of gene expression by lentiviral transduction in "human immune system" Rag2-/- gamma c -/- mice. METHODS MOL BIOL 2010;595:87-115 [PubMed]
Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H, Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC(+) CD127(+) natural killer-like cells. NAT IMMUNOL 2009;10 (1):66-74 [PubMed]
Finlay DK, Sinclair LV, Feijoo C, Waugh CM, Hagenbeek TJ, Spits H, Cantrell DA, Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes. J EXP MED 2009;206 (11):2441-2454 [PubMed]
Haridass D, Yuan Q, Becker PD, Cantz T, Iken M, Rothe M, Narain N, Bock M, Nörder M, Legrand N, Wedemeyer H, Weijer K, Spits H, Manns MP, Cai J, Deng H, Di Santo JP, Guzman CA, Ott M, Repopulation Efficiencies of Adult Hepatocytes, Fetal Liver Progenitor Cells, and Embryonic Stem Cell-Derived Hepatic Cells in Albumin-Promoter-Enhancer Urokinase-Type Plasminogen Activator Mice. AM J PATHOL 2009;175 (4):1483-1492 [PubMed]
Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K, Plet A, Corcuff E, Mortier E, Jacques Y, Spits H, Di Santo JP, IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J EXP MED 2009;206 (1):25-34 [PubMed]
Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, Debarry J, de Jong Y, Deng H, Di Santo JP, Eisenbarth S, Eynon E, Flavell RA, Guzman CA, Huntington ND, Kremsdorf D, Manns MP, Manz MG, Mention JJ, Ott M, Rathinam C, Rice CM, Rongvaux A, Stevens S, Spits H, Strick-Marchand H, Takizawa H, van Lent AU, Wang C, Weijer K, Willinger T, Ziegler P, Humanized mice for modeling human infectious disease: challenges, progress, and outlook. CELL HOST MICROBE 2009;6 (1):5-9 [PubMed]
ter Brake O, Legrand N, von Eije KJ, Centlivre M, Spits H, Weijer K, Blom B, Berkhout B, Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2(-/-)gammac(-/-)) mouse model. GENE THER 2009;16 (1):148-153 [PubMed]
Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H, Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. NAT IMMUNOL 2009;10 (8):864-871 [PubMed]
van Lent AU, Dontje W, Nagasawa M, Siamari R, Bakker AQ, Pouw SM, Maijoor KA, Weijer K, Cornelissen JJ, Blom B, Di Santo JP, Spits H, Legrand N, IL-7 Enhances Thymic Human T Cell Development in "Human Immune System" Rag2-/-IL-2R{gamma}c-/- Mice without Affecting Peripheral T Cell Homeostasis. J IMMUNOL 2009;183 (12):7645-7655 [PubMed]
van Lent AUG. Lymphoid development; a dynamic interplay of timing and dosing. s.l.: s.n.; 2009. 285p. ISBN 9789090244952 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Legrand N)
van Lent AUG, Centlivre M, Nagasawa M, Karrich J J., Pouw SM, Weijer K, Spits H, Blom B. In Vivo Modulation of gene expression by Lentiviral Transduction in "Human Immune System" Rag2-/-yc-/-Mice in: Naik SH, editor. Dendritic Cell Protocols. S.l.: Humana Press; 2009. Chapter 6, p. 87-115
Vivier E, Spits H, Cupedo T, Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair?. NAT REV IMMUNOL 2009;9 (4):229-234 [PubMed]
Diehl SA, Schmidlin H, Nagasawa M, van Haren SD, Kwakkenbos MJ, Yasuda E, Beaumont T, Scheeren FA, Spits H, STAT3-mediated up-regulation of BLIMP1 is coordinated with BCL6 down-regulation to control human plasma cell differentiation. J IMMUNOL 2008;180 (7):4805-4815 [PubMed]
Dontje W. From progenitor cell to immune cell: Cytokines and transcription factors in human hematopoietic development.. s.l.: s.n.; 2008. 187p. ISBN - [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Blom B; copromotor(s): )
Hagenbeek TJ. The role of the phosphatase Pten in T cell development. s.l.: s.n.; 2008. 178p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): )
Hagenbeek TJ, Spits H, T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus. LEUKEMIA 2008;22 (3):608-619 [PubMed]
Legrand N, Weijer K, Spits H, Experimental model for the study of the human immune system: production and monitoring of "human immune system" Rag2-/-gamma c-/- mice. METHODS MOL BIOL 2008;415:65-82 [PubMed]
Scheeren FA, Diehl SA, Smit LA, Beaumont T, Naspetti M, Bende RJ, Blom B, Karube K, Ohshima K, van Noesel CJM, Spits H, IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis. BLOOD 2008;111 (9):4706-4715 [PubMed]
Scheeren FA, Nagasawa M, Weijer K, Cupedo T, Kirberg J, Legrand N, Spits H, T cell-independent development and induction of somatic hypermutation in human IgM+ IgD+ CD27+ B cells. J EXP MED 2008;205 (9):2033-2042 [PubMed]
Schmidlin H. Transcriptional control of human plasmacytoid dendritic cell and B cell differentiation.. s.l.: s.n.; 2008. 189p. ISBN - [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H, Uittenbogaart CH; copromotor(s): Blom B)
Schmidlin H, Diehl SA, Nagasawa M, Scheeren FA, Schotte R, Uittenbogaart CH, Spits H, Blom B, Spi-B inhibits human plasma cell differentiation by repressing BLIMP1 and XBP-1 expression. BLOOD 2008;112 (5):1804-1812 [PubMed]
Sinclair LV, Finlay D, Feijoo C, Cornish GH, Gray A, Ager A, Okkenhaug K, Hagenbeek TJ, Spits H, Cantrell DA, Corrigendum: Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. NAT IMMUNOL 2008;9 (6):692 [PubMed]
Sinclair LV, Finlay D, Feijoo C, Cornish GH, Gray A, Ager A, Okkenhaug K, Hagenbeek TJ, Spits H, Cantrell DA, Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. NAT IMMUNOL 2008;9 (5):513-521 [PubMed]
An DS, Poon B, Tsong Fang RH, Weijer K, Blom B, Spits H, Chen ISY, Uittenbogaart CH, Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. CLIN VACCINE IMMUNOL 2007;14 (4):391-396 [PubMed]
Broers AEC, Bruinsma M, Posthumus-van Sluijs SJ, Wils EJ, Spits H, Lowenberg B, Braakman E, Cornelissen JJ, IL-7-mediated protection against minor-antigen-mismatched allograft rejection is associated with enhanced recovery of regulatory T cells. HAEMATOLOGICA 2007;92 (8):1099-1106 [PubMed]
Legrand N, Dontje W, van Lent AU, Spits H, Blom B, Human thymus regeneration and T cell reconstitution. SEMIN IMMUNOL 2007;19 (5):280-288 [PubMed]
Scheeren FA. Human B cell development and oncogenesis. s.l.: s.n.; 2007. 177p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): )
Schotte R. Control of early human lymphoid development. S.l.: s.n.; 2007. 148p. ISBN 9789090212191 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Blom B)
Spits H, Lanier LL, Natural killer or dendritic: what's in a name?. IMMUNITY 2007;26 (1):11-16 [PubMed]
van Lent AU, Nagasawa M, van Loenen MM, Schotte R, Schumacher TNM, Heemskerk MHM, Spits H, Legrand N, Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors. J IMMUNOL 2007;179 (8):4959-4968 [PubMed]
Wils EJ, Braakman E, Verjans GMGM, Rombouts EJC, Broers AEC, Niesters HGM, Wagemaker G, Staal FJT, Lowenberg B, Spits H, Cornelissen JJ, Flt3 ligand expands lymphoid progenitors prior to recovery of thymopoiesis and accelerates T cell reconstitution after bone marrow transplantation. J IMMUNOL 2007;178 (6):3551-3557 [PubMed]
Baba Y, Yokota T, Spits H, Garrett KP, Hayashi SI, Kincade PW, Constitutively active beta-catenin promotes expansion of multipotent hematopoietic progenitors in culture. J IMMUNOL 2006;177 (4):2294-2303 [PubMed]
Blom B, Spits H, Development of human lymphoid cells. ANNU REV IMMUNOL 2006;24:287-320 [PubMed]
Dontje W, Schotte R, Cupedo T, Nagasawa M, Scheeren F, Gimeno R, Spits H, Blom B, Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B. BLOOD 2006;107 (6):2446-2452 [PubMed]
Legrand N, Cupedo T, van Lent AU, Ebeli MJ, Weijer K, Hanke T, Spits H, Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in "human immune system" Rag2(-/-)gammac(-/-) mice. BLOOD 2006;108 (1):238-245 [PubMed]
Legrand N, Weijer K, Spits H, Experimental models to study development and function of the human immune system in vivo. J IMMUNOL 2006;176 (4):2053-2058 [PubMed]
Reits EA, Hodge JW, Herberts CA, Groothuis TA, Chakraborty M, Wansley EK, Camphausen K, Luiten RM, de Ru AH, Neijssen J, Griekspoor A, Mesman E, Verreck FA, Spits H, Schlom J, van Veelen P, Neefjes JJ, Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J EXP MED 2006;203 (5):1259-1271 [PubMed]
Schmidlin H, Dontje W, Groot F, Ligthart SJ, Colantonio AD, Oud ME, Schilder-Tol EJ, Spaargaren M, Spits H, Uittenbogaart CH, Blom B, Stimulated plasmacytoid dendritic cells impair human T-cell development. BLOOD 2006;108 (12):3792-3800 [PubMed]
Cupedo T, Nagasawa M, Weijer K, Blom B, Spits H, Development and activation of regulatory T cells in the human fetus. EUR J IMMUNOL 2005;35 (2):383-390 [PubMed]
Luiten RM, Kueter EWM, Mooi W, Gallee MPW, Rankin EM, Gerritsen WR, Clift SM, Nooijen WJ, Weder P, van de Kasteele WF, Sein J, van den Berk PCM, Nieweg OE, Berns AM, Spits H, de Gast GC, Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients. J CLIN ONCOL 2005;23 (35):8978-8991 [PubMed]
Scheeren FA, Naspetti M, Diehl S, Schotte R, Nagasawa M, Wijnands E, Gimeno R, Vyth-Dreese FA, Blom B, Spits H, STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression. NAT IMMUNOL 2005;6 (3):303-313 [PubMed]
drs Morra M. The X-linked lymphoproliferative syndrome: molecualr and cellular basis of the disease. S.l.: s.n.; 2004. 212p. ISBN - [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): )
Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N, Alves NL, Wijnands E, Blom B, Spits H, Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2-/- gammac-/- mice: functional inactivation of p53 in developing T cells. BLOOD 2004;104 (13):3886-3893 [PubMed]
Gurney KB, Colantonio AD, Blom B, Spits H, Uittenbogaart CH, Endogenous IFN-alpha production by plasmacytoid dendritic cells exerts an antiviral effect on thymic HIV-1 infection. J IMMUNOL 2004;173 (12):7269-7276 [PubMed]
Hagenbeek TJ, Naspetti M, Malergue F, Garçon F, Nunès JA, Cleutjens KBJM, Trapman J, Krimpenfort P, Spits H, The loss of PTEN allows TCR alphabeta lineage thymocytes to bypass IL-7 and Pre-TCR-mediated signaling. J EXP MED 2004;200 (7):883-894 [PubMed]
Schotte R, Nagasawa M, Weijer K, Spits H, Blom B, The ETS transcription factor Spi-B is required for human plasmacytoid dendritic cell development. J EXP MED 2004;200 (11):1503-1509 [PubMed]
Verra NCV, Jorritsma A, Weijer K, Ruizendaal JJ, Voordouw A, Weder P, Hooijberg E, Schumacher TNM, Haanen JBAG, Spits H, Luiten RM, Human telomerase reverse transcriptase-transduced human cytotoxic T cells suppress the growth of human melanoma in immunodeficient mice. CANCER RES 2004;64 (6):2153-2161 [PubMed]
Broers AEC, Posthumus-van Sluijs SJ, Spits H, van der Holt B, Löwenberg B, Braakman E, Cornelissen JJ, Interleukin-7 improves T-cell recovery after experimental T-cell-depleted bone marrow transplantation in T-cell-deficient mice by strong expansion of recent thymic emigrants. BLOOD 2003;102 (4):1534-1540 [PubMed]
Luiten RM, Péne J, Yssel H, Spits H, Ectopic hTERT expression extends the life span of human CD4(+) helper and regulatory T-cell clones and confers resistance to oxidative stress-induced apoptosis. BLOOD 2003;101 (11):4512-4519 [PubMed]
Roth A, Yssel H, Pene J, Chavez EA, Schertzer M, Lansdorp PM, Spits H, Luiten RM, Telomerase levels control the lifespan of human T lymphocytes. BLOOD 2003;102 (3):849-857 [PubMed]
Schotte R, Rissoan MC, Bendriss-Vermare N, Bridon JM, Duhen T, Weijer K, Brière F, Spits H, The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development. BLOOD 2003;101 (3):1015-1023 [PubMed]
van Rijn RS, Simonetti ER, Hagenbeek A, Hogenes MCH, de Weger RA, Canninga-van Dijk MR, Weijer K, Spits H, Storm G, van Bloois L, Rijkers G, Martens ACM, Ebeling SB, A new xenograft model for graft-versus-host disease by intravenous transfer of human peripheral blood mononuclear cells in RAG2-/- gammac-/- double-mutant mice. BLOOD 2003;102 (7):2522-2531 [PubMed]
Wolkers MC. Dissection of spontaneous and therapy-induced T cell immunity in mice. S.l.: s.n.; 2003. 104p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Spits H; copromotor(s): Schumacher TNJ)
Blom B, Ligthart SJWC, Schotte R, Spits H, Developmental origin of pre-DC2. HUM IMMUNOL 2002;63 (12):1072-1080 [PubMed]
Shvarts A, Brummelkamp TR, Scheeren F, Koh E, Daley GQ, Spits H, Bernards R, A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling. GENE DEV 2002;16 (6):681-686 [PubMed]
Spits H, Development of alphabeta T cells in the human thymus. NAT REV IMMUNOL 2002;2 (10):760-772 [PubMed]
van Montfrans C, Hooijberg E, Rodriguez Pena MS, de Jong EC, Spits H, te Velde AA, van Deventer SJH, Generation of regulatory gut-homing human T lymphocytes using ex vivo interleukin 10 gene transfer. GASTROENTEROLOGY 2002;123 (6):1877-1888 [PubMed]
Weijer K, Uittenbogaart CH, Voordouw A, Couwenberg F, Seppen J, Blom B, Vyth-Dreese FA, Spits H, Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo. BLOOD 2002;99 (8):2752-2759 [PubMed]
Yssel H, Spits H, Generation and maintenance of cloned human T cell lines. CURR PROTOC IMMUNOL 2002;Chapter 7:Unit 7.19 [PubMed]
Bukowski JF, Roncarolo MG, Spits H, Krangel MS, Morita CT, Brenner MB, Band H, T cell receptor-dependent activation of human lymphocytes through cell surface ganglioside GT1b: implications for innate immunity. EUR J IMMUNOL 2000;30 (11):3199-3206 [PubMed]
Dardalhon V, Jaleco S, Rebouissou C, Ferrand C, Skander N, Swainson L, Tiberghien P, Spits H, Noraz N, Taylor N, Highly efficient gene transfer in naive human T cells with a murine leukemia virus-based vector. BLOOD 2000;96 (3):885-893 [PubMed]
Galy A, Christopherson I, Ferlazzo G, Liu G, Spits H, Georgopoulos K, Distinct signals control the hematopoiesis of lymphoid-related dendritic cells. BLOOD 2000;95 (1):128-137 [PubMed]
Hooijberg E, Bakker AQ, Ruizendaal JJ, Spits H, NFAT-controlled expression of GFP permits visualization and isolation of antigen-stimulated primary human T cells. BLOOD 2000;96 (2):459-466 [PubMed]
Hooijberg E, Ruizendaal JJ, Snijders PJ, Kueter EW, Walboomers JM, Spits H, Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase. J IMMUNOL 2000;165 (8):4239-4245 [PubMed]
Kessels HW, van den Boom MD, Spits H, Hooijberg E, Schumacher TN, Changing T cell specificity by retroviral T cell receptor display. P NATL ACAD SCI USA 2000;97 (26):14578-14583 [PubMed]
Spits H, Couwenberg F, Bakker AQ, Weijer K, Uittenbogaart CH, Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J EXP MED 2000;192 (12):1775-1784 [PubMed]
Spits H, Res P, Jaleco AC, Techniques for studying development of human natural killer cells and T cells. METHODS MOL BIOL 2000;121:25-38 [PubMed]
van Oosterhout YV, van Emst L, Schattenberg AV, Tax WJ, Ruiter DJ, Spits H, Nagengast FM, Masereeuw R, Evers S, de Witte T, Preijers FW, A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease. BLOOD 2000;95 (12):3693-3701 [PubMed]
Blom B, Heemskerk MH, Verschuren MC, van Dongen JJ, Stegmann AP, Bakker AQ, Couwenberg F, Res PC, Spits H, Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors. EMBO J 1999;18 (10):2793-2802 [PubMed]
Blom B, Verschuren MC, Heemskerk MH, Bakker AQ, van Gastel-Mol EJ, Wolvers-Tettero IL, van Dongen JJ, Spits H, TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation. BLOOD 1999;93 (9):3033-3043 [PubMed]
Dardalhon V, Noraz N, Pollok K, Rebouissou C, Boyer M, Bakker AQ, Spits H, Taylor N, Green fluorescent protein as a selectable marker of fibronectin-facilitated retroviral gene transfer in primary human T lymphocytes. HUM GENE THER 1999;10 (1):5-14 [PubMed]
Heemskerk MH, Hooijberg E, Ruizendaal JJ, van der Weide MM, Kueter E, Bakker AQ, Schumacher TN, Spits H, Enrichment of an antigen-specific T cell response by retrovirally transduced human dendritic cells. CELL IMMUNOL 1999;195 (1):10-17 [PubMed]
Jacobs H, Krimpenfort P, Haks M, Allen J, Blom B, Démollière C, Kruisbeek A, Spits H, Berns A, PIM1 reconstitutes thymus cellularity in interleukin 7- and common gamma chain-mutant mice and permits thymocyte maturation in Rag- but not CD3gamma-deficient mice. J EXP MED 1999;190 (8):1059-1068 [PubMed]
Jaleco AC, Stegmann AP, Heemskerk MH, Couwenberg F, Bakker AQ, Weijer K, Spits H, Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3. BLOOD 1999;94 (8):2637-2646 [PubMed]
Pallard C, Stegmann AP, van Kleffens T, Smart F, Venkitaraman A, Spits H, Distinct roles of the phosphatidylinositol 3-kinase and STAT5 pathways in IL-7-mediated development of human thymocyte precursors. IMMUNITY 1999;10 (5):525-535 [PubMed]
Res PC, Couwenberg F, Vyth-Dreese FA, Spits H, Expression of pTalpha mRNA in a committed dendritic cell precursor in the human thymus. BLOOD 1999;94 (8):2647-2657 [PubMed]
Res P, Spits H, Developmental stages in the human thymus. SEMIN IMMUNOL 1999;11 (1):39-46 [PubMed]
Blom B, Res PC, Spits H, T cell precursors in man and mice. CRIT REV IMMUNOL 1998;18 (4):371-388 [PubMed]
Di Santo JP, Fehling HJ, Malissen B, Spits H, Borst J, Antigen receptors in lymphoid cell development and lymphocyte activation. RES IMMUNOL 1998;149 (9):868-871 [PubMed]
Martínez-Cáceres E, Jaleco AC, Res P, Noteboom E, Weijer K, Spits H, Characterization of CD34+ thymic stromal cells located in the subcapsular cortex of the human thymus. EXP HEMATOL 1998;26 (7):588-596 [PubMed]
Spits H, Blom B, Jaleco AC, Weijer K, Verschuren MC, van Dongen JJ, Heemskerk MH, Res PC, Early stages in the development of human T, natural killer and thymic dendritic cells. IMMUNOL REV 1998;165:75-86 [PubMed]
Verschuren MC, Blom B, Bogers AJ, Spits H, van Dongen JJ, PJA-BP expression and TCR delta deletion during human T cell differentiation. INT IMMUNOL 1998;10 (12):1873-1880 [PubMed]
Blom B, Res P, Noteboom E, Weijer K, Spits H, Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage. J IMMUNOL 1997;158 (8):3571-3577 [PubMed]
Bruno L, Res P, Dessing M, Cella M, Spits H, Identification of a committed T cell precursor population in adult human peripheral blood. J EXP MED 1997;185 (5):875-884 [PubMed]
Carbone E, Ruggiero G, Terrazzano G, Palomba C, Manzo C, Fontana S, Spits H, Kärre K, Zappacosta S, A new mechanism of NK cell cytotoxicity activation: the CD40-CD40 ligand interaction. J EXP MED 1997;185 (12):2053-2060 [PubMed]
Heemskerk MH, Blom B, Nolan G, Stegmann AP, Bakker AQ, Weijer K, Res PC, Spits H, Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J EXP MED 1997;186 (9):1597-1602 [PubMed]
Jaleco AC, Blom B, Res P, Weijer K, Lanier LL, Phillips JH, Spits H, Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells. J IMMUNOL 1997;159 (2):694-702 [PubMed]
Res P, Blom B, Hori T, Weijer K, Spits H, Downregulation of CD1 marks acquisition of functional maturation of human thymocytes and defines a control point in late stages of human T cell development. J EXP MED 1997;185 (1):141-151 [PubMed]
Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, van der Valk MA, Voordouw AC, Spits H, van Tellingen O, Zijlmans JM, Fibbe WE, Borst P, Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. P NATL ACAD SCI USA 1997;94 (8):4028-4033 [PubMed]
Chu DH, Spits H, Peyron JF, Rowley RB, Bolen JB, Weiss A, The Syk protein tyrosine kinase can function independently of CD45 or Lck in T cell antigen receptor signaling. EMBO J 1996;15 (22):6251-6261 [PubMed]
Lebedeva MI, Fields BA, Spits H, Panchamoorthy G, Brenner MB, Mariuzza RA, Cloning, expression, and crystallization of the V delta domain of a human gamma delta T-cell receptor. PROTEIN SCI 1996;5 (12):2638-2642 [PubMed]
Martinez-Cáceres E, Ruggiero G, Spits H, Juan M, Barceló J, Vives J, Martorell J, Viñas O, Stimulation through CD50 (ICAM-3) induces both activation and programmed cell death of human thymocytes. TISSUE ANTIGENS 1996;48 (6):626-635 [PubMed]
Res P, Martínez-Cáceres E, Cristina Jaleco A, Staal F, Noteboom E, Weijer K, Spits H, CD34+CD38dim cells in the human thymus can differentiate into T, natural killer, and dendritic cells but are distinct from pluripotent stem cells. BLOOD 1996;87 (12):5196-5206 [PubMed]
Ruggiero G, Cáceres EM, Voordouw A, Noteboom E, Graf D, Kroczek RA, Spits H, CD40 expressed on thymic epithelial cells provides costimulation for proliferation but not for apoptosis of human thymocytes. J IMMUNOL 1996;156 (10):3737-3746 [PubMed]
Staal FJ, Bakker AQ, Verkuijlen M, van Oort E, Spits H, Use of bicistronic retroviral vectors encoding the LacZ gene together with a gene of interest: a method to select producer cells and follow transduced target cells. CANCER GENE THER 1996;3 (5):345-351 [PubMed]
Bárcena A, Muench MO, Roncarolo MG, Spits H, Tracing the expression of CD7 and other antigens during T- and myeloid-cell differentiation in the human fetal liver and thymus. LEUKEMIA LYMPHOMA 1995;17 (1-2):1-11 [PubMed]
Spits H, Lanier LL, Phillips JH, Development of human T and natural killer cells. BLOOD 1995;85 (10):2654-2670 [PubMed]
Staal FJ, Res PC, Weijer K, Spits H, Development of retrovirally marked human T progenitor cells into mature thymocytes. INT IMMUNOL 1995;7 (8):1301-1309 [PubMed]
Bárcena A, Galy AH, Punnonen J, Muench MO, Schols D, Roncarolo MG, de Vries JE, Spits H, Lymphoid and myeloid differentiation of fetal liver CD34+lineage- cells in human thymic organ culture. J EXP MED 1994;180 (1):123-132 [PubMed]
Bárcena A, Muench MO, Roncarolo MG, Spits H, In search of T-cell progenitors in the human foetal liver. RES IMMUNOL 1994;145 (2):120-3; discussion 155-8 [PubMed]
Hintzen RQ, Lens SM, Koopman G, Pals ST, Spits H, van Lier RA, CD70 represents the human ligand for CD27. INT IMMUNOL 1994;6 (3):477-480 [PubMed]
Spits H, Early stages in human and mouse T-cell development. CURR OPIN IMMUNOL 1994;6 (2):212-221 [PubMed]
Spits H, Bárcena A, Hori T, Sánchez MJ, Phillips JH, Galy A, Early events in human intrathymic T-cell development. RES IMMUNOL 1994;145 (2):128-34; discussion 155-8 [PubMed]
Vandekerckhove BA, Bárcena A, Schols D, Mohan-Peterson S, Spits H, Roncarolo MG, In vivo cytokine expression in the thymus. CD3high human thymocytes are activated and already functionally differentiated in helper and cytotoxic cells. J IMMUNOL 1994;152 (4):1738-1743 [PubMed]
Azuma M, Yssel H, Phillips JH, Spits H, Lanier LL, Functional expression of B7/BB1 on activated T lymphocytes. J EXP MED 1993;177 (3):845-850 [PubMed]
Bacchetta R, Vandekerckhove BA, Touraine JL, Bigler M, Martino S, Gebuhrer L, de Vries JE, Spits H, Roncarolo MG, Chimerism and tolerance to host and donor in severe combined immunodeficiencies transplanted with fetal liver stem cells. J CLIN INVEST 1993;91 (3):1067-1078 [PubMed]
Bárcena A, Muench MO, Galy AH, Cupp J, Roncarolo MG, Phillips JH, Spits H, Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development. BLOOD 1993;82 (11):3401-3414 [PubMed]
de Waal Malefyt R, Verma S, Bejarano MT, Ranes-Goldberg M, Hill M, Spits H, CD2/LFA-3 or LFA-1/ICAM-1 but not CD28/B7 interactions can augment cytotoxicity by virus-specific CD8+ cytotoxic T lymphocytes. EUR J IMMUNOL 1993;23 (2):418-424 [PubMed]
Galy AH, de Waal Malefyt R, Barcena A, Peterson SM, Spits H, Untransfected and SV40-transfected fetal and postnatal human thymic stromal cells. Analysis of phenotype, cytokine gene expression and cytokine production. THYMUS 1993;22 (1):13-33 [PubMed]
Galy AH, Spits H, Hamilton JA, Regulation of M-CSF production by cultured human thymic epithelial cells. LYMPHOKINE CYTOKINE RES 1993;12 (5):265-270 [PubMed]
Galy A, Verma S, Bárcena A, Spits H, Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. J EXP MED 1993;178 (2):391-401 [PubMed]
Mutis T, Kraakman EM, Cornelisse YE, Haanen JB, Spits H, de Vries RR, Ottenhoff TH, Analysis of cytokine production by Mycobacterium-reactive T cells. Failure to explain Mycobacterium leprae-specific nonresponsiveness of peripheral blood T cells from lepromatous leprosy patients. J IMMUNOL 1993;150 (10):4641-4651 [PubMed]
Ranes-Goldberg MG, Hori T, Mohan-Peterson S, Spits H, Identification of human pre-T/NK cell-associated genes. J IMMUNOL 1993;151 (10):5810-5821 [PubMed]
Sánchez MJ, Spits H, Lanier LL, Phillips JH, Human natural killer cell committed thymocytes and their relation to the T cell lineage. J EXP MED 1993;178 (6):1857-1866 [PubMed]
Touraine JL, Roncarolo MG, Plotnicky H, Bachetta R, Spits H, T lymphocytes from human chimeras do recognize antigen in the context of allogeneic determinants of the major histocompatibility complex. IMMUNOL LETT 1993;39 (1):9-12 [PubMed]
Yssel H, Schneider P, Spits H, Production of IL4 by human T cells and regulation of differentiation of T-cell subsets by IL4. RES IMMUNOL 1993;144 (8):610-616 [PubMed]
de Waal Malefyt R, Yssel H, Roncarolo MG, Spits H, de Vries JE, Interleukin-10. CURR OPIN IMMUNOL 1992;4 (3):314-320 [PubMed]
Galy AH, Spits H, CD40 is functionally expressed on human thymic epithelial cells. J IMMUNOL 1992;149 (3):775-782 [PubMed]
Gascan H, Aversa GG, Gauchat JF, van Vlasselaer P, Roncarolo MG, Yssel H, Kehry M, Spits H, de Vries JE, Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta or TcR gamma delta induce IgE synthesis by human B cells in the presence of interleukin-4. EUR J IMMUNOL 1992;22 (5):1133-1141 [PubMed]
Hori T, Phillips JH, Duncan B, Lanier LL, Spits H, Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL-4, or IL-7: implications for the relationship between T and natural killer cells. BLOOD 1992;80 (5):1270-1278 [PubMed]
Hsu DH, Moore KW, Spits H, Differential effects of IL-4 and IL-10 on IL-2-induced IFN-gamma synthesis and lymphokine-activated killer activity. INT IMMUNOL 1992;4 (5):563-569 [PubMed]
Lanier LL, Chang C, Spits H, Phillips JH, Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. J IMMUNOL 1992;149 (6):1876-1880 [PubMed]
Lanier LL, Spits H, Phillips JH, The developmental relationship between NK cells and T cells. IMMUNOL TODAY 1992;13 (10):392-395 [PubMed]
Momburg F, Ortiz-Navarrete V, Neefjes J, Goulmy E, van de Wal Y, Spits H, Powis SJ, Butcher GW, Howard JC, Walden P, Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation. NATURE 1992;360 (6400):174-177 [PubMed]
Phillips JH, Hori T, Nagler A, Bhat N, Spits H, Lanier LL, Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins. J EXP MED 1992;175 (4):1055-1066 [PubMed]
Spits H, de Waal Malefyt R, Functional characterization of human IL-10. INT ARCH ALLERGY IMM 1992;99 (1):8-15 [PubMed]
Yssel H, de Waal Malefyt R, Roncarolo MG, Abrams JS, Lahesmaa R, Spits H, de Vries JE, IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J IMMUNOL 1992;149 (7):2378-2384 [PubMed]
Alexandre D, Chuchana P, Roncarolo MG, Yssel H, Spits H, Lefranc G, Lefranc MP, Reciprocal hybrid joints demonstrate successive V-J rearrangements on the same chromosome in the human TCR gamma locus. INT IMMUNOL 1991;3 (10):973-982 [PubMed]
de Vries JE, de Waal Malefyt R, Yssel H, Roncarolo MG, Spits H, Do human TH1 and TH2 CD4+ clones exist?. RES IMMUNOL 1991;142 (1):59-63 [PubMed]
de Waal Malefyt R, Haanen J, Spits H, Roncarolo MG, te Velde A, Figdor C, Johnson K, Kastelein R, Yssel H, de Vries JE, Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J EXP MED 1991;174 (4):915-924 [PubMed]
Galy AH, Spits H, IL-1, IL-4, and IFN-gamma differentially regulate cytokine production and cell surface molecule expression in cultured human thymic epithelial cells. J IMMUNOL 1991;147 (11):3823-3830 [PubMed]
Gascan H, Gauchat JF, Roncarolo MG, Yssel H, Spits H, de Vries JE, Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J EXP MED 1991;173 (3):747-750 [PubMed]
Haanen JB, de Waal Malefijt R, Res PC, Kraakman EM, Ottenhoff TH, de Vries RR, Spits H, Selection of a human T helper type 1-like T cell subset by mycobacteria. J EXP MED 1991;174 (3):583-592 [PubMed]
Hori T, Cupp J, Wrighton N, Lee F, Spits H, Identification of a novel human thymocyte subset with a phenotype of CD3- CD4+ CD8 alpha + beta-1. Possible progeny of the CD3- CD4- CD8- subset. J IMMUNOL 1991;146 (12):4078-4084 [PubMed]
Hori T, de Waal Malefyt R, Duncan BW, Harrison MR, Roncarolo MG, Spits H, Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 delta and epsilon but not membrane CD3. INT IMMUNOL 1991;3 (4):353-357 [PubMed]
Hori T, Paliard X, de Waal Malefijt R, Ranes M, Spits H, Comparative analysis of CD8 expressed on mature CD4+ CD8+ T cell clones cultured with IL-4 and that on CD8+ T cell clones: implication for functional significance of CD8 beta. INT IMMUNOL 1991;3 (7):737-741 [PubMed]
Hori T, Spits H, Characterization of triple negative clones isolated from post-natal human thymus. ADV EXP MED BIOL 1991;292:97-104 [PubMed]
Hori T, Spits H, Clonal analysis of human CD4-CD8-CD3- thymocytes highly purified from postnatal thymus. J IMMUNOL 1991;146 (7):2116-2121 [PubMed]
Morita CT, Verma S, Aparicio P, Martinez C, Spits H, Brenner MB, Functionally distinct subsets of human gamma/delta T cells. EUR J IMMUNOL 1991;21 (12):2999-3007 [PubMed]
O'Hehir RE, Yssel H, Verma S, de Vries JE, Spits H, Lamb JR, Clonal analysis of differential lymphokine production in peptide and superantigen induced T cell anergy. INT IMMUNOL 1991;3 (8):819-826 [PubMed]
Paliard X, de Vries JE, Spits H, Comparison of lymphokine secretion and responsiveness of human T cell clones isolated in IL-4 and in IL-2. CELL IMMUNOL 1991;135 (2):383-393 [PubMed]
Peyron JF, Verma S, de Waal Malefyt R, Sancho J, Terhorst C, Spits H, The CD45 protein tyrosine phosphatase is required for the completion of the activation program leading to lymphokine production in the Jurkat human T cell line. INT IMMUNOL 1991;3 (12):1357-1366 [PubMed]
Phillips JH, McKinney L, Azuma M, Spits H, Lanier LL, A novel beta 4, alpha 6 integrin-associated epithelial cell antigen involved in natural killer cell and antigen-specific cytotoxic T lymphocyte cytotoxicity. J EXP MED 1991;174 (6):1571-1581 [PubMed]
Roncarolo MG, Bacchetta R, Bigler M, Touraine JL, de Vries JE, Spits H, A SCID patient reconstituted with HLA-incompatible fetal stem cells as a model for studying transplantation tolerance. BLOOD CELLS 1991;17 (2):391-402 [PubMed]
Roncarolo MG, Bigler M, Haanen JB, Yssel H, Bacchetta R, de Vries JE, Spits H, Natural killer cell clones can efficiently process and present protein antigens. J IMMUNOL 1991;147 (3):781-787 [PubMed]
Spertini F, Spits H, Geha RS, Staphylococcal exotoxins deliver activation signals to human T-cell clones via major histocompatibility complex class II molecules. P NATL ACAD SCI USA 1991;88 (17):7533-7537 [PubMed]
Spits H, Human T cell receptor gamma delta + T cells. SEMIN IMMUNOL 1991;3 (2):119-129 [PubMed]
Spits H, Paliard X, Vandekerckhove Y, van Vlasselaer P, de Vries JE, Functional and phenotypic differences between CD4+ and CD4- T cell receptor-gamma delta clones from peripheral blood. J IMMUNOL 1991;147 (4):1180-1188 [PubMed]
Spits H, Yssel H, Brockelhurst C, Krangel M, Evidence for controlled gene rearrangements and cytokine production during development of human TCR gamma delta+ lymphocytes. CURR TOP MICROBIOL 1991;173:47-55 [PubMed]
Vandekerckhove BA, Krowka JF, McCune JM, de Vries JE, Spits H, Roncarolo MG, Clonal analysis of the peripheral T cell compartment of the SCID-hu mouse. J IMMUNOL 1991;146 (12):4173-4179 [PubMed]
Bacchetta R, de Waal Malefijt R, Yssel H, Abrams J, de Vries JE, Spits H, Roncarolo MG, Host-reactive CD4+ and CD8+ T cell clones isolated from a human chimera produce IL-5, IL-2, IFN-gamma and granulocyte/macrophage-colony-stimulating factor but not IL-4. J IMMUNOL 1990;144 (3):902-908 [PubMed]
de Waal Malefyt R, Yssel H, Spits H, de Vries JE, Sancho J, Terhorst C, Alarcon B, Human T cell leukemia virus type I prevents cell surface expression of the T cell receptor through down-regulation of the CD3-gamma, -delta, -epsilon, and -zeta genes. J IMMUNOL 1990;145 (7):2297-2303 [PubMed]
Haanen JB, Ottenhoff TH, Lai A Fat RF, Soebono H, Spits H, de Vries RR, Mycobacterium leprae-specific T cells from a tuberculoid leprosy patient suppress HLA-DR3-restricted T cell responses to an immunodominant epitope on 65-kDa hsp of mycobacteria. J IMMUNOL 1990;145 (11):3898-3904 [PubMed]
Hsu DH, de Waal Malefyt R, Fiorentino DF, Dang MN, Vieira P, de Vries J, Spits H, Mosmann TR, Moore KW, Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1. SCIENCE 1990;250 (4982):830-832 [PubMed]
Krangel MS, Yssel H, Brocklehurst C, Spits H, A distinct wave of human T cell receptor gamma/delta lymphocytes in the early fetal thymus: evidence for controlled gene rearrangement and cytokine production. J EXP MED 1990;172 (3):847-859 [PubMed]
Spits H, Paliard X, Engelhard VH, de Vries JE, Cytotoxic activity and lymphokine production of T cell receptor (TCR)-alpha beta+ and TCR-gamma delta+ cytotoxic T lymphocyte (CTL) clones recognizing HLA-A2 and HLA-A2 mutants. Recognition of TCR-gamma delta+ CTL clones is affected by mutations at positions 152 and 156. J IMMUNOL 1990;144 (11):4156-4162 [PubMed]
Spits H, Touraine JL, Yssel H, de Vries JE, Roncarolo MG, Presence of host-reactive and MHC-restricted T cells in a transplanted severe combined immunodeficient (SCID) patient suggest positive selection and absence of clonal deletion. IMMUNOL REV 1990;116:101-116 [PubMed]
Spits H, Yssel H, de Vries JE, Analysis of antigen specificity of human TCR gamma delta + T cells. RES IMMUNOL 1990;141 (7):636-640 [PubMed]
Trounstine ML, Peltz GA, Yssel H, Huizinga TW, von dem Borne AE, Spits H, Moore KW, Reactivity of cloned, expressed human Fc gamma RIII isoforms with monoclonal antibodies which distinguish cell-type-specific and allelic forms of Fc gamma RIII. INT IMMUNOL 1990;2 (4):303-310 [PubMed]
Blanchard D, Aubry JP, de Vries JE, Spits H, The role of Ca2+ and Mg2+ in the cytotoxic T lymphocyte reaction and in the secretion of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester-serine esterase by human T cell clones. J IMMUNOL 1989;142 (7):2173-2180 [PubMed]
de Vries JE, Yssel H, Spits H, Interplay between the TCR/CD3 complex and CD4 or CD8 in the activation of cytotoxic T lymphocytes. IMMUNOL REV 1989;109:119-141 [PubMed]
de Waal Malefyt R, Alarcon B, Yssel H, Sancho J, Miyajima A, Terhorst CP, Spits H, de Vries JE, Introduction of T cell receptor (TCR)-alpha cDNA has differential effects on TCR-gamma delta/CD3 expression by PEER and Lyon-1 cells. J IMMUNOL 1989;142 (10):3634-3642 [PubMed]
Hata S, Clabby M, Devlin P, Spits H, de Vries JE, Krangel MS, Diversity and organization of human T cell receptor delta variable gene segments. J EXP MED 1989;169 (1):41-57 [PubMed]
Paliard X, Yssel H, Blanchard D, Waitz JA, deVries JE, Spits H, Antigen specific and MHC nonrestricted cytotoxicity of T cell receptor alpha beta+ and gamma delta+ human T cell clones isolated in IL-4. J IMMUNOL 1989;143 (2):452-457 [PubMed]
Rousset F, Billaud M, Blanchard D, Figdor C, Lenoir GM, Spits H, de Vries JE, IL-4 induces LFA-1 and LFA-3 expression on Burkitt's lymphoma cell lines. Requirement of additional activation by phorbol myristate acetate for induction of homotypic cell adhesions. J IMMUNOL 1989;143 (5):1490-1498 [PubMed]
Spits H, Paliard X, de Vries JE, Antigen-specific, but not natural killer, activity of T cell receptor-gamma delta cytotoxic T lymphocyte clones involves secretion of N alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester serine esterase and influx of Ca2+ ions. J IMMUNOL 1989;143 (5):1506-1511 [PubMed]
Spits H, Yssel H, de Vries JE, The induction of T cell-mediated cytolysis by monoclonal antibodies against the T cell receptor/CD3 complex. INT REV IMMUNOL 1989;4 (2):115-132 [PubMed]
Yssel H, de Waal Malefyt R, Duc Dodon MD, Blanchard D, Gazzolo L, de Vries JE, Spits H, Human T cell leukemia/lymphoma virus type I infection of a CD4+ proliferative/cytotoxic T cell clone progresses in at least two distinct phases based on changes in function and phenotype of the infected cells. J IMMUNOL 1989;142 (7):2279-2289 [PubMed]
Baer R, Boehm T, Yssel H, Spits H, Rabbitts TH, Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments. EMBO J 1988;7 (6):1661-1668 [PubMed]
Blanchard D, van Els C, Aubry JP, de Vries JE, Spits H, CD4 is involved in a post-binding event in the cytolytic reaction mediated by human CD4+ cytotoxic T lymphocyte clones. J IMMUNOL 1988;140 (6):1745-1752 [PubMed]
Bonnefoy JY, Guillot O, Spits H, Blanchard D, Ishizaka K, Banchereau J, The low-affinity receptor for IgE (CD23) on B lymphocytes is spatially associated with HLA-DR antigens. J EXP MED 1988;167 (1):57-72 [PubMed]
Fleischer B, Sturm E, de Vries JE, Spits H, Triggering of cytotoxic T lymphocytes and NK cells via the Tp103 pathway is dependent on the expression of the T cell receptor/CD3 complex. J IMMUNOL 1988;141 (4):1103-1107 [PubMed]
Hochstenbach F, Parker C, McLean J, Gieselmann V, Band H, Bank I, Chess L, Spits H, Strominger JL, Seidman JG, Characterization of a third form of the human T cell receptor gamma/delta. J EXP MED 1988;168 (2):761-776 [PubMed]
Paliard X, de Waal Malefijt R, Yssel H, Blanchard D, Chrétien I, Abrams J, de Vries J, Spits H, Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J IMMUNOL 1988;141 (3):849-855 [PubMed]
Paliard X, Malefijt RW, de Vries JE, Spits H, Interleukin-4 mediates CD8 induction on human CD4+ T-cell clones. NATURE 1988;335 (6191):642-644 [PubMed]
Pène J, Rousset F, Brière F, Chrétien I, Bonnefoy JY, Spits H, Yokota T, Arai N, Arai K, Banchereau J, IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. P NATL ACAD SCI USA 1988;85 (18):6880-6884 [PubMed]
Pène J, Rousset F, Brière F, Chrétien I, Paliard X, Banchereau J, Spits H, de Vries JE, IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma. J IMMUNOL 1988;141 (4):1218-1224 [PubMed]
Roncarolo MG, Yssel H, Touraine JL, Bacchetta R, Gebuhrer L, de Vries JE, Spits H, Antigen recognition by MHC-incompatible cells of a human mismatched chimera. J EXP MED 1988;168 (6):2139-2152 [PubMed]
Roncarolo MG, Yssel H, Touraine JL, Betuel H, de Vries JE, Spits H, Autoreactive T cell clones specific for class I and class II HLA antigens isolated from a human chimera. J EXP MED 1988;167 (5):1523-1534 [PubMed]
Satyanarayana K, Hata S, Devlin P, Roncarolo MG, de Vries JE, Spits H, Strominger JL, Krangel MS, Genomic organization of the human T-cell antigen-receptor alpha/delta locus. P NATL ACAD SCI USA 1988;85 (21):8166-8170 [PubMed]
Spits H, Yssel H, Paliard X, Kastelein R, Figdor C, de Vries JE, IL-4 inhibits IL-2-mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes in mixed leukocyte cultures. J IMMUNOL 1988;141 (1):29-36 [PubMed]
van Seventer GA, Spits H, Yssel H, Melief CJ, Ivanyi P, Differential recognition by human cytotoxic T cell clones of human M1 fibroblasts transfected with an HLA-B7 gene (JY150) suggests the existence of two different HLA-B7 alleles in the cell line JY (HLA-A2,2;B7,7;Cw-,-;DR4,w6). J IMMUNOL 1988;141 (2):417-422 [PubMed]
van Seventer GA, van Lier RA, Kuijpers KC, Spits H, Melief CJ, Regulatory role of the CD8 antigen in both CD3 and CD2 monoclonal antibody-induced nonspecific cytotoxicity of class I- and class II-allospecific cytotoxic T cell clones. EUR J IMMUNOL 1988;18 (12):1973-1978 [PubMed]
Yokota T, Arai N, de Vries J, Spits H, Banchereau J, Zlotnik A, Rennick D, Howard M, Takebe Y, Miyatake S, Molecular biology of interleukin 4 and interleukin 5 genes and biology of their products that stimulate B cells, T cells and hemopoietic cells. IMMUNOL REV 1988;102:137-187 [PubMed]
Alarcon B, de Vries J, Pettey C, Boylston A, Yssel H, Terhorst C, Spits H, The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone. P NATL ACAD SCI USA 1987;84 (11):3861-3865 [PubMed]
Blanchard D, van Els C, Borst J, Carrel S, Boylston A, de Vries JE, Spits H, The role of the T cell receptor, CD8, and LFA-1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones. J IMMUNOL 1987;138 (8):2417-2421 [PubMed]
Borst J, de Vries E, Spits H, de Vries JE, Boylston AW, Matthews EA, Complexity of T cell receptor recognition sites for defined alloantigens. J IMMUNOL 1987;139 (6):1952-1959 [PubMed]
Spits H, Yssel H, Takebe Y, Arai N, Yokota T, Lee F, Arai K, Banchereau J, de Vries JE, Recombinant interleukin 4 promotes the growth of human T cells. J IMMUNOL 1987;139 (4):1142-1147 [PubMed]
Yssel H, Aubry JP, de Waal Malefijt R, de Vries JE, Spits H, Regulation by anti-CD2 monoclonal antibody of the activation of a human T cell clone induced by anti-CD3 or anti-T cell receptor antibodies. J IMMUNOL 1987;139 (9):2850-2855 [PubMed]
Yssel H, de Vries JE, Borst J, Spits H, Distribution and functional analysis of a 120- to 130-kDa T-cell surface antigen. CELL IMMUNOL 1987;105 (1):161-173 [PubMed]
Borst J, Boylston AW, de Vries JE, Spits H, Human T cell lines differing in phenotype and specificity are reactive with the same anti-idiotypic antibody. J IMMUNOL 1986;136 (2):601-608 [PubMed]
Borst J, Spits H, Voordouw A, de Vries E, Boylston A, de Vries JE, A family of T-cell receptor molecules expressed on T-cell clones with different specificities for allomajor histocompatibility antigens. HUM IMMUNOL 1986;17 (4):426-442 [PubMed]
Boylston AW, Borst J, Yssel H, Blanchard D, Spits H, de Vries JE, Properties of a panel of monoclonal antibodies which react with the human T cell antigen receptor on the leukemic line HPB-ALL and a subset of normal peripheral blood T lymphocytes. J IMMUNOL 1986;137 (2):741-744 [PubMed]
de Vries JE, Keizer GD, te Velde AA, Voordouw A, Ruiter D, Rümke P, Spits H, Figdor CG, Characterization of melanoma-associated surface antigens involved in the adhesion and motility of human melanoma cells. INT J CANCER 1986;38 (4):465-473 [PubMed]
Haanen JB, Ottenhoff TH, Voordouw A, Elferink BG, Klatser PR, Spits H, de Vries RR, HLA class-II-restricted Mycobacterium leprae-reactive T-cell clones from leprosy patients established with a minimal requirement for autologous mononuclear cells. SCAND J IMMUNOL 1986;23 (1):101-108 [PubMed]
Spits H, van Schooten W, Keizer H, van Seventer G, van de Rijn M, Terhorst C, de Vries JE, Alloantigen recognition is preceded by nonspecific adhesion of cytotoxic T cells and target cells. SCIENCE 1986;232 (4748):403-405 [PubMed]
Stam NJ, Spits H, Ploegh HL, Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J IMMUNOL 1986;137 (7):2299-2306 [PubMed]
Terhorst C, de Vries J, Georgopoulos K, Gold D, Oettgen H, Pettey C, Spits H, Ucker D, van den Elsen P, Wileman T, The T cell receptor/T3 complex. YEAR IMMUNOL 1986;2:245-253 [PubMed]
van Seventer GA, van Lier RA, Spits H, Ivanyi P, Melief CJ, Evidence for a regulatory role of the T8 (CD8) antigen in antigen-specific and anti-T3-(CD3)-induced lytic activity of allospecific cytotoxic T lymphocyte clones. EUR J IMMUNOL 1986;16 (11):1363-1371 [PubMed]
Yssel H, Blanchard D, Boylston A, de Vries JE, Spits H, T cell clones which share T cell receptor epitopes differ in phenotype, function and specificity. EUR J IMMUNOL 1986;16 (10):1187-1193 [PubMed]
Bosch ML, Schreuder GM, Spits H, Termijtelen A, Tilanus MG, Giphart MJ, Polymorphisms within the HLA-DRw6 haplotype. I. Restriction fragment length variation and its correlation with serology. J IMMUNOL 1985;134 (5):3212-3217 [PubMed]
Keizer GD, Borst J, Figdor CG, Spits H, Miedema F, Terhorst C, de Vries JE, Biochemical and functional characteristics of the human leukocyte membrane antigen family LFA-1, Mo-1 and p150,95. EUR J IMMUNOL 1985;15 (11):1142-1148 [PubMed]
Leeuwenberg JF, Spits H, Tax WJ, Capel PJ, Induction of nonspecific cytotoxicity by monoclonal anti-T3 antibodies. J IMMUNOL 1985;134 (6):3770-3775 [PubMed]
Spits H, Borst J, Tax W, Capel PJ, Terhorst C, de Vries JE, Characteristics of a monoclonal antibody (WT-31) that recognizes a common epitope on the human T cell receptor for antigen. J IMMUNOL 1985;135 (3):1922-1928 [PubMed]
Spits H, Yssel H, Leeuwenberg J, de Vries JE, Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. EUR J IMMUNOL 1985;15 (1):88-91 [PubMed]
Spits H, Yssel H, Voordouw A, de Vries JE, The role of T8 in the cytotoxic activity of cloned cytotoxic T lymphocyte lines specific for class II and class I major histocompatibility complex antigens. J IMMUNOL 1985;134 (4):2294-2298 [PubMed]
Arnaout MA, Spits H, Terhorst C, Pitt J, Todd RF 3rd, Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo1 deficiency. Effects of cell activation on Mo1/LFA-1 surface expression in normal and deficient leukocytes. J CLIN INVEST 1984;74 (4):1291-1300 [PubMed]
Bernabeu C, Maziarz R, Spits H, de Vries J, Burakoff SJ, Terhorst C, Coexpression of the human HLA-A2 or HLA-B7 heavy chain gene and human beta 2-microglobulin gene in L cells. J IMMUNOL 1984;133 (6):3188-3194 [PubMed]
Breuning MH, Spits H, de Vries JE, Iványi P, A cloned cytotoxic T-lymphocyte (CTL) line recognizing a subtype of HLA B27. HUM IMMUNOL 1984;9 (4):231-242 [PubMed]
de Vries JE, Spits H, Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J IMMUNOL 1984;132 (1):510-519 [PubMed]
Miedema F, Tetteroo PA, Hesselink WG, Werner G, Spits H, Melief CJ, Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity). EUR J IMMUNOL 1984;14 (6):518-523 [PubMed]
Spits H, Borst J, Giphart M, Coligan J, Terhorst C, de Vries JE, HLA-DC antigens can serve as recognition elements for human cytotoxic T lymphocytes. EUR J IMMUNOL 1984;14 (4):299-304 [PubMed]
Taketani S, Krangel MS, Spits H, de Vries J, Strominger JL, Structural analysis of an HLA-B7 antigen variant detected by cytotoxic T lymphocytes. J IMMUNOL 1984;133 (2):816-821 [PubMed]
van de Rijn M, Bernabeu C, Royer-Pokora B, Weiss J, Seidman JG, de Vries J, Spits H, Terhorst C, Recognition of HLA-A2 by cytotoxic T lymphocytes after DNA transfer into human and murine cells. SCIENCE 1984;226 (4678):1083-1085 [PubMed]
Yssel H, de Vries JE, Koken M, van Blitterswijk W, Spits H, Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J IMMUNOL METHODS 1984;72 (1):219-227 [PubMed]
Yssel H, Spits H, de Vries JE, A cloned human T cell line cytotoxic for autologous and allogeneic B lymphoma cells. J EXP MED 1984;160 (1):239-254 [PubMed]
Bernabeu C, Finlay D, van de Rijn M, Maziarz RT, Biro PA, Spits H, de Vries J, Terhorst CP, Expression of the major histocompatibility antigens HLA-A2 and HLA-B7 by DNA-mediated gene transfer. J IMMUNOL 1983;131 (4):2032-2037 [PubMed]
Borst J, Spits H, de Vries J, Pessano S, Rovera G, Terhorst C, Target antigen of monoclonal reagent S5.7: comparison with T3 antigen. HYBRIDOMA 1983;2 (3):265-274 [PubMed]
de Vries JE, Vyth-Dreese FA, Figdor CG, Spits H, Leemans JM, Bont WS, Induction of phenotypic differentiation, interleukin 2 production, and PHA responsiveness of "immature" human thymocytes by interleukin 1 and phorbol ester. J IMMUNOL 1983;131 (1):201-206 [PubMed]
Snow P, Spits H, de Vries J, Terhorst C, Comparison of target antigens of monoclonal reagents OKT5, OKT8, and Leu2A, which inhibit effector function of human cytotoxic T lymphocytes. HYBRIDOMA 1983;2 (2):187-199 [PubMed]
Spits H, Ijssel H, Thompson A, de Vries JE, Human T4+ and T8+ cytotoxic T lymphocyte clones directed at products of different class II major histocompatibility complex loci. J IMMUNOL 1983;131 (2):678-683 [PubMed]
Spits H, Keizer G, Borst J, Terhorst C, Hekman A, de Vries JE, Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines. HYBRIDOMA 1983;2 (4):423-437 [PubMed]
Terhorst C, Borst J, Lerch P, van de Rijn M, Snow P, Spits H, de Vries J, Structural and functional aspects of the T-cell differentiation antigens T3, T6, and T8. HAEMATOL BLOOD TRANSFUS 1983;28:440-446 [PubMed]
de Vries JE, Vyth-Dreese FA, van der Hulst R, Sminia P, Figdor CG, Bont WS, Spits H, The replacement of monocytes and interleukin-1 by phorbol ester in lectin-induced proliferation of human thymocytes and T cells. IMMUNOBIOLOGY 1982;162 (2):103-115 [PubMed]
Figdor CG, Vyth-Dreese FA, Bont WS, Spits H, de Vries JE, Isolation of human thymocytes differing in maturation state and function by centrifugal elutriation. THYMUS 1982;4 (4):243-256 [PubMed]
Spits H, Borst J, Terhorst C, de Vries JE, The role of T cell differentiation markers in antigen-specific and lectin-dependent cellular cytotoxicity mediated by T8+ and T4+ human cytotoxic T cell clones directed at class I and class II MHC antigens. J IMMUNOL 1982;129 (4):1563-1569 [PubMed]
Spits H, Breuning M, Ivanyi P, Russo C, de Vries JE, In vitro-isolated human cytotoxic T-lymphocyte clones detect variations in serologically defined HLA antigens. IMMUNOGENETICS 1982;16 (6):503-512 [PubMed]
Spits H, Ijssel H, Terhorst C, de Vries JE, Establishment of human T lymphocyte clones highly cytotoxic for an EBV-transformed B cell line in serum-free medium: isolation of clones that differ in phenotype and specificity. J IMMUNOL 1982;128 (1):95-99 [PubMed]
Spits H, de Vries JE, Terhorst C, A permanent human cytotoxic T-cell line with high killing capacity against a lymphoblastoid B-cell line shows preference for HLA A, B target antigens and lacks spontaneous cytotoxic activity. CELL IMMUNOL 1981;59 (2):435-447 [PubMed]
Spits H, de Vries JE, Terhorst C, The cell-mediated lympholysis-inducing capacity of highly purified human monocytes and T lymphocytes in primary and secondary mixed leukocyte cultures. J IMMUNOL 1981;126 (6):2275-2278 [PubMed]
Opperdoes FR, Borst P, Spits H, Particle-bound enzymes in the bloodstream form of Trypanosoma brucei. EUR J BIOCHEM 1977;76 (1):21-28 [PubMed]
Temmink JH, Collard JG, Spits H, Roos E, A comparative study of four cytochemical detection methods of concanavalin A binding sites on the cell membrane. EXP CELL RES 1975;92 (2):307-322 [PubMed]
Key publications

Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H, Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. NAT IMMUNOL 2009;10 (8):864-871 [PubMed]
Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjösberg JM, Spits H, Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. NAT IMMUNOL 2013;14 (3):221-229 [PubMed]
Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Vivier E, Innate lymphoid cells--a proposal for uniform nomenclature. NAT REV IMMUNOL 2013;13 (2):145-149 [PubMed]
Artis D, Spits H, The biology of innate lymphoid cells. NATURE 2015;517 (7534):293-301 [PubMed]
Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H, Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. NAT IMMUNOL 2011;12 (11):1055-1062 [PubMed]


All Publications

Curriculum Vitae

 Dr. Spits has a 35 years-spanning career in both academia and industry. He is a professor of Cell Biology at the Academic Center of the University of Amsterdam (AMC) where he leads a research program on auto immune- and inflammatory diseases. He is also a founder of AIMM Therapeutics, a company that develops human monoclonal antibodies for treatment of diseases with a high unmet medical need and serves as its CSO since its inception. Previously Dr. Spits was a Senior Director at Genentech where he implemented and directed drug discovery in the Cancer Immunotherapy area and led the large molecule drug discovery efforts in the area of auto immune- and inflammatory diseases. Before joining Genentech Dr. Spits was professor Cell Biology at the AMC. Prior to that Dr. Spits was at the Netherlands Cancer Institute where he was a senior staff scientist and served as Head of the Immunology Department. From 1985 through 1992 Dr. Spits held several positions at Schering-Plough, first at the Schering–Plough Institute for Immunological Research in Lyon and then at the DNAX Research Institute for Molecular Biological Research in Palo Alto in California. Dr. Spits earned his PhD degree at the University of Amsterdam and conducted research at the Dana Farber Institute for Cancer Research, Harvard University. He authored more than 300 peer-reviewed scientific publications.

During his career Spits has made important contributions to the field of human lymphocytes. He was the first (in 1985) to describe the phenomenon of redirected killing by human T cells using anti CD3 antibodies. This breakthough discovery forms the basis of therapeutic bispecific antibodies that are currently tested in the clinic for treatment of various forms of cancer.  When at DNAX he was one of the first to describe human Th1 clones. He studied the mechanisms of human T cell development and identified a number of previously not recognized intermediate cell stages in human thymic development. More recent contributions include the first description of Th22 and the discovery of human Lymphoid Tissue inducer cell and various other human Innate Lymphoid cell subsets. While studying the mechanisms of development of human antibody-producing B cells his lab invented an innovative technology to immortalize human and non-human antibody-producing B cells which was used by the company AIMM therapeutics to establish a number of broadly reacting highly neutralizing virus specific antibodies, some of which are in clinical development. Currently Spits investigates the function of Innate lymphoid cells at mucosal tissues, in particular lung and gut. In addition he works in the field of tumor immunology. One of his projects aims to generate therapeutic human monoclonal antibodies against melanoma. His research is supported by various grants including a 5 year advanced grant of the European Research Council.  

Spits has been named a 2015 Thomson Reuters Highly Cited Reseacher (ranked among the top 1% of researchers of most cited documents in their specific field)

Research programmes

The biology of human Innate Lymphoid Cells and B cells. Antibodies against tumor antigens

Targeting human rhinoviruses and group 2 ILC in asthma exacerbations

Asthma constitutes a group of debilitating chronic diseases that affects millions of people worldwide, profoundly impacting patient quality of life and incurring large costs in terms of treatment and lost productivity. In particular so called asthma exacerbations induced by respiratory viruses such as human Rhinovirus and respiratory syncytial virus present significant unmet medical need. Successful discovery and development of more effective therapies to treat asthma exacerbations depends first on a better understanding of the underlying mechanisms, including how proinflammatory cells proliferate unchecked, and how the body’s own mechanisms might be enlisted to control inflammation and second on inhibition of exacerbating respiratory viruses. My group is addressing this challenge in two ways. First, we have discovered and characterized populations of innate lymphoid cells (ILCs) including ILCs that produce high amounts of Th2 cytokines (ILC2) and demonstrated amplified numbers of these cells in inflamed nose polyps in rhinosinusitis, a chronic type 2 inflammatory disease. Second, our group has developed a technological breakthrough that permits the establishment of clonal, antigen-specific human B cell lines using a unique genetic reprogramming technology. Using this technology we have generated broadly reacting, highly neutralizing, human monoclonal antibodies against respiratory syncytial virus and influenza virus. We hypothesize that ILC2 activated by respiratory viruses are key players in asthma exacerbations induced by these viruses and are therefore compelling targets for effective therapies for asthma. Our objectives are to identify the key drivers of function of ILC2 and to develop broadly reacting highly neutralizing antibodies against human rhinovirus (HRV) which accounts for the majority of asthma exacerbations. In addressing these objectives, we make use of extensive expertise in fundamental human immunology with groundbreaking, translational approaches using human tissue biopsy samples, state-of-the-art in vitro techniques, and a human immune system mouse model developed by our laboratory that permits in vivo study of the human immune system.

ILC in the human Intestine

ILC play important roles in innate immunity, maintenance of tissue homeostasis and tissue repair after damage inflicted by pathogens. Our group investigates development and function of ILC populations present in different compartnments present in non-inflamed intestine and in intestines of patients suffering Inflammatory Bowel diseases, in particular Crohn's disease and Ulcerative Colitis. The ultimate goal is to determine whether these cells play a role in the pathology. If so the knowledge acquired in this project can result in new therapies targeting ILC.

Characterization of immortalized human B cells

We have developed a highly efficient platform to generate human monoclonal antibodies. The platform uses B cells immortalized by genetic modification. We also have set up a mouse model with a rudimentary human immune system; the so called human immune system (HIS) mouse. B cells develop in these mice but those cells do not mature. In this project we investigate how we can optimise B cell maturation in HIS. If successful this project will provide tools to optimally test the response of human immune cells against vaccines in vivo and to make fully human monoclonal antibodies against clinical targets following immunization.

Human monoclonal antibodies against tumor antigens

Immunotherapies such as treatment with checkpoint inhibitors such as antibodies against PD-1 and CTLA4 have a major impact on survival in a number of cancers, particular melanoma.  Whereas  the role of T cells in the immuneresponse against cancer cells following checkpoint inhibition is well established, the role of B cells and the antibodies they produce has not yet been systematically studied. We hypothesize that B cells of patients who successfully respond to immunotherapy produce antibodies that contribute to the tumor free status of these patients. Such antibodies may have therapeutic utility. In collaboration with Dr Mette Hazenberg of the department of Hematology, Dr Rosalie Luiten of the department of dermatology of the AMC and the AMC spin out company AIMM Therapeutics we establish B cell clones from patients with a durable remission following immunotherapy. We focus on Melanoma patients tretead with cellular therapies or with checkpoint inhibitors and on Acute Myeloid Leukemia patients treated with allogeneic stem cell transplatation. From peripheral blood B cells of these patients we establish immortalized B cell clones and screen these clones for production of antibodies that specifically react with tumor cells. A number of tumor-specific antibodies have been generated which are now tested for their potential to reduce tumor growth 

 

Faculty
Prof. dr. H. Spits

Postdocs
Dr. S.M. Bal PhD
Dr. J.M. Bernink MSc
Dr. J.R. Fergusson
Drs. K. Golebski
Dr. B.A. Heesters
Dr. J. Romero-Ros
Dr. M.M. Shikhagaie PhD

PhD Students
L. Bartels
Drs. M.A. Gillissen MD
Drs. G. de Jong MD (AIMM Therapeutics)
L. Krabbendam
Y.F. van Lier
S.J.L. Merat MSc
M. Nagasawa

Other research related activities
  • Scientific manager, AIMM therapeutics
Current research funding
  • AMC
  • Europese Unie
  • Janssen Research & Development, LLC
  • Medical Research BV
  • MedImmune LLC
  • Pfizer Inc.
  • Universiteit Leiden
  • ZonMw (Vrijgesteld)