• Principal Investigator
  • Male

Dr. M.A. Nolte

Position: Scientific staff member (UD)
Main activities: Research
Specialisation: Cross-talk between immune activation and hematopoiesis
foto M.A. Nolte is one of the AMC Principal Investigators
Focus of research:

My Adaptive Immunity Lab at the department of Hematopoiesis at Sanquin has two major research interests:

1. The impact of immune activation on hematopoiesis In this research line we investigate the mechanism by which the intricate process of hematopoiesis can be influenced by the activated immune system. Hematopoiesis occurs in the confined niches of the bone marrow, where hematopoietic stem cells differentiate to mature blood cells. This process is tightly controlled by local feedback mechanisms, as growth factors and stromal cells regulate bone marrow output. However, we have identified a new immune cell-mediated feedback mechanism, in which cells of the activated immune system also influence cell differentiation in the bone marrow to improve the host’s immunity. We anticipate that more insight in this feedback mechanism will provide better understanding of the consequences of (chronic) immune activation on blood cell formation, which could lead to better therapeutic strategies and facilitate the generation of blood cell products.

2. The molecular mechanism of effector T cell formation We also wish to obtain insight in the mechanisms that direct the generation and maintenance of memory and effector T cells that protect against (persistent) viruses. Hence we focus on the impact of costimulatory molecules in this process, such as CD27 and GITR. Moreover, we also investigate the role of transcription factors in effector T cell formation, amongst which the recently identified molecule HOBIT, a close relative of BLIMP-1. Both human and mouse studies are being conducted to address these issues. By performing these experiments we hope to better understand the requirements for generating memory and effector T cells and apply this knowledge in the development of adoptive T cell therapy. 
 

AMC themes: Infection & Immunity
Departments: Landsteiner Laboratory
Geerman S, Nolte MA, Impact of T cells on hematopoietic stem and progenitor cell function: Good guys or bad guys?. WORLD J STEM CELLS 2017;9 (2):37-44 [PubMed]
Hartholt RB, Wroblewska A, Herczenik E, Peyron I, ten Brinke A, Rispens T, Nolte MA, Slot E, Claassens JW, Nimmerjahn F, Verbeek JS, Voorberg J, Enhanced uptake of blood coagulation factor VIII containing immune complexes by antigen presenting cells. J THROMB HAEMOST 2017;15 (2):329-340 [PubMed]
Vasanthakumar A, Liao Y, teh P, Pascutti MF, Oja AE, Garnham AL, Gloury R, Tempany JC, Sidwell T, Cuadrado E, Tuijnenburg P, Kuijpers TW, Lalaoui N, Mielke LA, Bryant VL, Hodgkin PD, Silke J, Smyth GK, Nolte MA, Shi W, Kallies A, The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues. CELL REP 2017;ahead of print [PubMed]
Geerman S, Hickson S, Brasser G, Pascutti MF, Nolte MA, Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae. FRONT IMMUNOL 2016;6:660 [PubMed]
Meiler S, Smeets E, Winkels H, Shami A, Pascutti MF, Nolte MA, Beckers L, Weber C, Gerdes N, Lutgens E, Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report. ARTERIOSCL THROM VAS 2016;36 (9):1748-1752 [PubMed]
Olivier BJ, Cailotto C, van der Vliet J, Knippenberg M, Greuter MJ, Hilbers FW, Konijn T, te Velde AA, Nolte MA, Boeckxstaens GE, de Jonge WJ, Mebius RE, Vagal innervation is required for the formation of tertiary lymphoid tissue in colitis. EUR J IMMUNOL 2016;46 (10):2467-2480 [PubMed]
Pascutti MF, Erkelens MN, Nolte MA, Impact of Viral Infections on Hematopoiesis: From Beneficial to Detrimental Effects on Bone Marrow Output. FRONT IMMUNOL 2016;7:364 [PubMed]
Cornelissen AS, Maijenburg MW, Nolte MA, Voermans C, Organ-specific migration of mesenchymal stromal cells: Who, when, where and why?. IMMUNOL LETT 2015;168 (2):159-169 [PubMed]
Pascutti MF, Geerman S, Slot E, van Gisbergen KPJM, Boon L, Arens R, van Lier RAW, Wolkers MC, Nolte MA, Enhanced CD8 T cell responses through GITR-mediated costimulation resolve chronic viral infection. PLOS PATHOG 2015;11 (3):e1004675 [PubMed]
Vieira Braga FA, Hertoghs KML, Kragten NAM, Doody GM, Barnes NA, Remmerswaal EBM, Hsiao CC, Moerland PD, Wouters D, Derks IAM, van Stijn A, Demkes M, Hamann J, Eldering E, Nolte MA, Tooze RM, ten Berge IJM, van Gisbergen KPJM, van Lier RAW, Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans. EUR J IMMUNOL 2015;45 (10):2945-2958 [PubMed]
Costes LMM, van der Vliet J, Farro G, Matteoli G, van Bree SHW, Olivier BJ, Nolte MA, Boeckxstaens GE, Cailotto C, The spleen responds to intestinal manipulation but does not participate in the inflammatory response in a mouse model of postoperative ileus. PLOS ONE 2014;9 (7):e102211 [PubMed]
de Bruin AM, Voermans C, Nolte MA, Impact of interferon-γ on hematopoiesis. BLOOD 2014;124 (16):2479-2486 [PubMed]
Libregts SFWM, Nolte MA, Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow. EXP CELL RES 2014;329 (2):239-247 [PubMed]
Nolte MA, SLPI is essential for granulopoiesis. BLOOD 2014;123 (8):1121-1123 [PubMed]
Nolte MA, van der Meer JWM, Inflammatory responses to infection: the Dutch contribution. IMMUNOL LETT 2014;162 (2 Part B):113-120 [PubMed]
de Bruin AM, Demirel Ö, Hooibrink B, Brandts CH, Nolte MA, Interferon-gamma impairs proliferation of hematopoietic stem cells in mice. BLOOD 2013;121 (18):3578-3585 [PubMed]
Francosalinas G, Cantaert T, Nolte MA, Tak PP, van Lier RAW, Baeten DL, Enhanced costimulation by CD70+ B cells aggravates experimental autoimmune encephalomyelitis in autoimmune mice. J NEUROIMMUNOL 2013;255 (1-2):8-17 [PubMed]
Koning JJ, Kooij G, de Vries HE, Nolte MA, Mebius RE, Mesenchymal stem cells are mobilized from the bone marrow during inflammation. FRONT IMMUNOL 2013;4:UNSP 49 [PubMed]
Libregts SFWM. Immune activation and lineage fate decisions: inducing a shift of program. s.l.: s.n.; 2013. 200p. ISBN 9789461918529 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): van Lier RAW; copromotor(s): Nolte MA)
Nolte MA, van Lier RAW, With(out) a little help from my friends: an IL-12/CD40L-mediated feed-forward loop between CD8+ T cells and DCs. EUR J IMMUNOL 2013;43 (6):1445-1448 [PubMed]
Vink PM, Smout WM, Driessen-Engels LJ, de Bruin AM, Delsing D, Krajnc-Franken MA, Jansen AJ, Rovers EF, van Puijenbroek AA, Kaptein A, Nolte MA, Garritsen A, van Eenennaam H, In vivo knockdown of TAK1 accelerates bone marrow proliferation/differentiation and induces systemic inflammation. PLOS ONE 2013;8 (3):e57348 [PubMed]
Wensveen FM, Geest CR, Libregts SFWM, Derks IAM, Ekert PG, Labi V, Villunger A, Nolte MA, Eldering E, BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis. APOPTOSIS 2013;18 (11):1306-1318 [PubMed]
Xiao Y, Song JY, de Vries TJ, Fatmawati C, Parreira DB, Langenbach GEJ, Babala N, Nolte MA, Everts V, Borst J, Osteoclast precursors in murine bone marrow express CD27 and are impeded in osteoclast development by CD70 on activated immune cells. P NATL ACAD SCI USA 2013;110 (30):12385-12390 [PubMed]
de Bruin AM. Hematopoietic remoddeling during immune activation: connecting hematopoiesis. s.l.: s.n.; 2012. 152p. [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): van Lier RAW; copromotor(s): Nolte MA)
de Bruin AM, Libregts SF, Valkhof M, Boon L, Touw IP, Nolte MA, IFN gamma induces monopoiesis and inhibits neutrophil development during inflammation. BLOOD 2012;119 (6):1543-1554 [PubMed]
van Gisbergen KPJM, Kragten NAM, Hertoghs KML, Wensveen FM, Jonjic S, Hamann J, Nolte MA, van Lier RAW, Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. NAT IMMUNOL 2012;13 (9):864-871 [PubMed]
Wensveen FM, Derks IAM, van Gisbergen KPJM, de Bruin AM, Meijers JCM, Yigittop H, Nolte MA, Eldering E, van Lier RAW, BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation. BLOOD 2012;119 (6):1440-1449 [PubMed]
Libregts SF, Gutiérrez L, de Bruin AM, Wensveen FM, Papadopoulos P, van Ijcken W, Ozgür Z, Philipsen S, Nolte MA, Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. BLOOD 2011;118 (9):2578-2588 [PubMed]
Libregts S, van Olffen RW, van der Sluijs KF, van Lier RAW, Nolte MA, Function of CD27 in helper T cell differentiation. IMMUNOL LETT 2011;136 (2):177-186 [PubMed]
Samsom JN, van Ham SM, Toes REM, Bos NA, Damoiseaux J, van Baarle D, van de Loosdrecht AA, Nolte MA, Guiding the action of the immune system: Interactions between the immune system and non-immune tissues: NVVI-Dutch society for Immunology Course, Lunteren, March 31st-April 1st, 2010. IMMUNOL LETT 2011;138 (1):1-3 [PubMed]
van Gisbergen KPJM, Klarenbeek PL, Kragten NAM, Unger PPA, Nieuwenhuis MBB, Wensveen FM, ten Brinke A, Tak PP, Eldering E, Nolte MA, van Lier RAW, The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. IMMUNITY 2011;35 (1):97-108 [PubMed]
Abreu JRF, Krausz S, Dontje W, Grabiec AM, de Launay D, Nolte MA, Tak PP, Reedquist KA, Sustained T cell Rap1 signaling is protective in the collagen-induced arthritis model of rheumatoid arthritis. ARTHRITIS RHEUM-US 2010;62 (11):3289-3299 [PubMed]
de Bruin AM, Buitenhuis M, van der Sluijs KF, van Gisbergen KPJM, Boon L, Nolte MA, Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-gamma. BLOOD 2010;116 (14):2559-2569 [PubMed]
van Olffen RW, de Bruin AM, Vos M, Staniszewska AD, Hamann J, van Lier RAW, de Vries CJM, Nolte MA, CD70-Driven Chronic Immune Activation Is Protective against Atherosclerosis. J INNATE IMMUN 2010;2 (4):344-352 [PubMed]
Beishuizen CRL, Kragten NAM, Boon L, Nolte MA, van Lier RAW, van Gisbergen KPJM, Chronic CD70-driven costimulation impairs IgG responses by instructing T cells to inhibit germinal center B cell formation through FasL-Fas interactions. J IMMUNOL 2009;183 (10):6442-6451 [PubMed]
Joffre O, Nolte MA, Spörri R, Reis e Sousa C, Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. IMMUNOL REV 2009;227 (1):234-247 [PubMed]
Nolte MA, van Olffen RW, van Gisbergen KPJM, van Lier RAW, Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology. IMMUNOL REV 2009;229 (1):216-231 [PubMed]
van Gisbergen KPJM, van Olffen RW, van Beek J, van der Sluijs KF, Arens R, Nolte MA, van Lier RA, Protective CD8 T Cell Memory Is Impaired during Chronic CD70-Driven Costimulation. J IMMUNOL 2009;182 (9):5352-5362 [PubMed]
van Olffen RW. Modulating T cell homeostasis via TNF and TNFR superfamily members. "Characterization and function of effector & regulatory T cells". s.l.: s.n.; 2009. 235p. ISBN 9789090247274 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): van Lier RAW; copromotor(s): Nolte MA)
van Olffen RW, Koning N, van Gisbergen KPJM, Wensveen FM, Hoek RM, Boon L, Hamann J, van Lier RAW, Nolte MA, GITR triggering induces expansion of both effector and regulatory CD4+ T cells in vivo. J IMMUNOL 2009;182 (12):7490-7500 [PubMed]
Nolte MA, Leibundgut-Landmann S, Joffre O, Reis e Sousa C, Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo. J EXP MED 2007;204 (6):1487-1501 [PubMed]
Nolte MA, van Lier RAW, The price of the CD27-CD70 costimulatory axis: you can't have it all. J EXP MED 2006;203 (11):2405-2408 [PubMed]
Wieland CW, Kerver ME, Florquin S, Nolte MA, Borst J, van Lier R, van Oers MHJ, van der Poll T, CD27 contributes to the early systemic immune response to Mycobacterium tuberculosis infection but does not affect outcome. INT IMMUNOL 2006;18 (11):1531-1539 [PubMed]
Nolte MA, Arens R, van Os R, van Oosterwijk M, Hooibrink B, van Lier RAW, van Oers MHJ, Immune activation modulates hematopoiesis through interactions between CD27 and CD70. NAT IMMUNOL 2005;6 (4):412-418 [PubMed]
Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, Schweighoffer E, Williams DL, Gordon S, Tybulewicz VL, Brown GD, Reis e Sousa C, Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. IMMUNITY 2005;22 (4):507-517 [PubMed]
Schulz O, Diebold SS, Chen M, Näslund TI, Nolte MA, Alexopoulou L, Azuma YT, Flavell RA, Liljeström P, Reis e Sousa C, Toll-like receptor 3 promotes cross-priming to virus-infected cells. NATURE 2005;433 (7028):887-892 [PubMed]
Arens R, Nolte MA, Tesselaar K, Heemskerk B, Reedquist KA, van Lier RAW, van Oers MHJ, Signaling through CD70 regulates B cell activation and IgG production. J IMMUNOL 2004;173 (6):3901-3908 [PubMed]
Arens R, Schepers K, Nolte MA, van Oosterwijk MF, van Lier RAW, Schumacher TNM, van Oers MHJ, Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J EXP MED 2004;199 (11):1595-1605 [PubMed]
Kater AP, Remmerswaal EBM, Nolte MA, Eldering E, van Oers MHJ, van Lier RAW, Autologous cytomegalovirus-specific T cells as effector cells in immunotherapy of B cell chronic lymphocytic leukaemia. BRIT J HAEMATOL 2004;126 (4):512-516 [PubMed]
Mebius RE, Nolte MA, Kraal G, Development and function of the splenic marginal zone. CRIT REV IMMUNOL 2004;24 (6):449-464 [PubMed]
Nolte MA, Arens R, Kraus M, van Oers MHJ, Kraal G, van Lier RAW, Mebius RE, B cells are crucial for both development and maintenance of the splenic marginal zone. J IMMUNOL 2004;172 (6):3620-3627 [PubMed]
Nolte MA, Kraal G, Mebius RE, Effects of fluorescent and nonfluorescent tracing methods on lymphocyte migration in vivo. CYTOM PART A 2004;61 (1):35-44 [PubMed]
Nolte MA, Beliën JAM, Schadee-Eestermans I, Jansen W, Unger WWJ, van Rooijen N, Kraal G, Mebius RE, A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp. J EXP MED 2003;198 (3):505-512 [PubMed]
de Jonge WJ, Kwikkers KL, te Velde AA, van Deventer SJH, Nolte MA, Mebius RE, Ruijter JM, Lamers MC, Lamers WH, Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice. J CLIN INVEST 2002;110 (10):1539-1548 [PubMed]
Geijtenbeek TBH, Groot PC, Nolte MA, van Vliet SJ, Gangaram-Panday ST, van Duijnhoven GCF, Kraal G, van Oosterhout AJM, van Kooyk Y, Marginal zone macrophages express a murine homologue of DC-SIGN that captures blood-borne antigens in vivo. BLOOD 2002;100 (8):2908-2916 [PubMed]
Nolte MA, Hamann A, Kraal G, Mebius RE, The strict regulation of lymphocyte migration to splenic white pulp does not involve common homing receptors. IMMUNOLOGY 2002;106 (3):299-307 [PubMed]
Nolte MA, Hoen EN, van Stijn A, Kraal G, Mebius RE, Isolation of the intact white pulp. Quantitative and qualitative analysis of the cellular composition of the splenic compartments. EUR J IMMUNOL 2000;30 (2):626-634 [PubMed]
Elisen MG, van Kooij RJ, Nolte MA, Marquart JA, Lock TM, Bouma BN, Meijers JC, Protein C inhibitor may modulate human sperm-oocyte interactions. BIOL REPROD 1998;58 (3):670-677 [PubMed]
Key publications

de Bruin AM, Demirel Ö, Hooibrink B, Brandts CH, Nolte MA, Interferon-gamma impairs proliferation of hematopoietic stem cells in mice. BLOOD 2013;121 (18):3578-3585 [PubMed]
van Gisbergen KPJM, Kragten NAM, Hertoghs KML, Wensveen FM, Jonjic S, Hamann J, Nolte MA, van Lier RAW, Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. NAT IMMUNOL 2012;13 (9):864-871 [PubMed]
de Bruin AM, Voermans C, Nolte MA, Impact of interferon-γ on hematopoiesis. BLOOD 2014;124 (16):2479-2486 [PubMed]
Pascutti MF, Geerman S, Slot E, van Gisbergen KPJM, Boon L, Arens R, van Lier RAW, Wolkers MC, Nolte MA, Enhanced CD8 T cell responses through GITR-mediated costimulation resolve chronic viral infection. PLOS PATHOG 2015;11 (3):e1004675 [PubMed]
de Bruin AM, Libregts SF, Valkhof M, Boon L, Touw IP, Nolte MA, IFN gamma induces monopoiesis and inhibits neutrophil development during inflammation. BLOOD 2012;119 (6):1543-1554 [PubMed]


All Publications

Curriculum Vitae

2011-present

  • Principal Investigator/Head of Laboratory: Sanquin Research, Amsterdam, The Netherlands
  • Lab: Adaptive Immunity Lab
  • Department: Hematopoiesis
  • Department head: Dr. Marieke von Lindern
  • Research focus: T cell Immunity and its Impact on Hematopoieis.

2006 - 2011:

  • Principal Investigator: Academic Medical Center, Amsterdam, The Netherlands
  • Lab head: Prof. Dr. R. van Lier
  • Department: Experimental Immunology
  • Research focus: The Influence of the Activated Immune System on Hematopoieis.

2004 - 2006:

  • Postdoctoral fellow (EMBO Long-term fellowship): Cancer Research UK, London, United Kingdom
  • Lab head: Dr. C. Reis e Sousa
  • Department: Immunobiology Lab
  • Research topic: Dendritic Cells and their Environment.

2002 - 2004:

  • Postdoctoral fellow: Academic Medical Center, Amsterdam, The Netherlands
  • Lab head: Prof. Dr. R. van Oers / Prof. Dr. R. van Lier
  • Department: Hematology / Experimental Immunology
  • Research topic: The Function of CD27 on Hematopoietic Stem Cells.

1997 - 2002

  • Doctorate: Free University, Amsterdam, The Netherlands
  • Promotor: Prof. Dr. G. Kraal
  • Copromotor: Dr. R.E. Mebius
  • Department: Molecular Cell Biology, VU Medical Center
  • Title of thesis: Compartments, Cells and Molecules in the Spleen.
  • Thesis defense: 1st March 2002
Research programmes

Impact of Immune Activation on Hematopoiesis

Research grants over last 10 years:

  • 2004: Visualisation of DC function in vivo. (EMBO Long-term Fellowship)
  • 2006: Immune cells go back home: hematopoietic regulation through immune activation. (ZonMW VIDI)
  • 2006: Bone marrow exposed: immunological impact on hematopoietic regulation. (LSBR research grant)
  • 2008: The cells that rock the cradle: the impact of effector lymphocytes on hematopoiesis in the bone marrow. (FCT Fellowship, Portugal)
  • 2010: T cell modulation of hematopoiesis. (LSBR Fellowship)
  • 2010: Nanoscale analysis of signal transduction in normal and malignant hematopoietic (stem) cells. (NWO Medium Sized Investment Application; co-applicant)
  • 2013: Joined forces: Understanding and rebuilding the vascular bone marrow niche. (PPOc Program)

Faculty
Dr. M.A. Nolte (Sanquin)

Postdocs
Dr. M.F. Pascutti

PhD Students
Drs. S.C. Geerman (Sanquin)
Drs. M.J. Goedhart (Sanquin)
A.E. Oja

Others
Ing. E.M. Slot (Sanquin)

Other research related activities
  • Membership of medical or scientific committee, ZonMw (Netherlands Organisation for Health Research and Development), ZonMW VENI committee
  • Contribution to training of professionals, VU University Medical Center
  • Membership of medical or scientific committee, Dutch Society for Immunology, Secretary of the program-committee of the annual Immunology Course
  • Speakers bureau / Lectures, University of Amsterdam
Current research funding
  • None reported