Martijn (M. A.) Nolte PhD




‘Compartments, Cells and Molecules in the Spleen’
Promotor: Prof G Kraal PhD
Copromotor: RE Mebius PhD
1 March 2002 - Department of Molecular Cell Biology, VU Medical Center, Amsterdam

Research interests

Operating within the department of Hematopoiesis, the Adaptive Immunity Lab 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.


  • Flow cytometry and cell sorting
  • Cell culture of primary hematopoietic progenitors
  • HSC transplantations in mice
  • Quantitative PCR, ELISA, Western blotting,
  • T cell stimulation (in vitro and in vivo)
  • NKT cell analysis
  • Viral infection models in mice with LCMV, MCMV and Influenza virus


Educational activities

2011-present Head of The Adaptive Immunity Lab at the Dept of Hematopoiesis, Sanquin Research
2006-2010 Staff member at the Dept of Experimental Immunology, AMC, Amsterdam
2004-2006 EMBO Fellow at the Immunobiology Lab, Cancer Research UK, London, UK
2002-2004 Postdoctoral fellow at the Dept of Experimental Immunology, AMC, Amsterdam
1997-2002 PhD student at the Dept of Molecular Cell Biology, VUMC, Amsterdam
1997 Graduated in Medical Biology, Utrecht University, Utrecht

2010-present Lecturer for the Bachelor course ‘Immunology’ for Science students of the Amsterdam University College
2008-2011 Coordinator and lecturer for the Bachelor course ‘Clinical and Experimental Immunology’ for second year medical students at the AMC, Amsterdam
2007-present Lecturer for the Master course ‘Advanced Immunology’ for students Biomedical Sciences of the University of Amsterdam
2006-2011 Lecturer for the Bachelor course 'Infectious Diseases, Immunity and Inflammation' for medical students at the AMC, Amsterdam
2002-present Lecturer for the Advanced Immunology PhD Course

Other activities

2010-present Member of the course committee of the Advanced Immunology PhD Course
2010-present Member of the NWO-ZonMw VENI committee
2009-present Member (secretary) of the program-committee of the NVVI Lunteren Course

Other publications

Samsom JN, Marieke van Ham SM, Toes RE, 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. Immunology Letters 2011; 138(1):1-3.

Libregts SF, van Olffen RW, van der Sluijs KF, van Lier RAW, Nolte MA. Function of CD27 in helper T cell differentiation. Immunology Letters 2011; 136(2):177-86.

Libregts SF, Gutierrez L, de Bruin AM, Wensveen FM, Papadopoulos P, van Ijcken W, Ozgur Z, Philipsen S, Nolte MA. Chronic IFN{gamma} production in mice induces anemia by reducing erythrocyte lifespan and inhibiting erythropoiesis through an IRF-1/PU.1-axis. Blood 2011; 118(9):2578-2588. abstract

De Bruin AM, Buitenhuis M, van der Sluijs KF, van Gisbergen KP, Boon L, Nolte MA. Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-gamma. Blood 2010; 116(14):2559-69.

Abreu JR, 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 & Rheumatism 2010; 62(11):3289-99.

Van Olffen RW, de Bruin AM, Vos M, Staniszewska AD, Hamann J, van Lier RA, de Vries CJ, Nolte MA. CD70-driven immune activation is protective against atherosclerosis. Journal of Innate Immunity 2010; 2(4):344-52.

Nolte MA
, van Olffen RW, van Gisbergen KP, van Lier RA. 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):216-31. Review.

Van Olffen RW, Koning N, van Gisbergen KP, Wensveen FM, Hoek RM, Boon L, Hamann J, van Lier RA, Nolte MA. GITR triggering induces expansion of both effector and regulatory CD4+ T cells in vivo. J Immunol 2009; 182(12):7490-500.

Beishuizen CR, Kragten NA, Boon L, Nolte MA, van Lier RA, van Gisbergen KP. 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):6442-51.

Van Gisbergen KP, 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):5352-62.

Joffre O#, Nolte MA#, Spörri R#, Reis e Sousa C. Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunological Reviews 2009; 227(1):234-47. (# Equally contributed)

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. Journal of Experimental Medicine 2007; 204(6):1487-501.

Nolte MA
, van Lier RA. The price of the CD27-CD70 costimulatory axis: you can't have it all. Journal of Experimental Medicine 2006; 203(11):2405-8.

Wieland CW, Kerver ME, Florquin S, Nolte MA, Borst J, van Lier R, van Oers MH, van der Poll T. CD27 contributes to the early systemic immune response to Mycobacterium tuberculosis infection but does not affect outcome. International Immunology 2006; 18(11):1531-9.

Nolte MA
, Arens R, van Os R, van Oosterwijk M, Hooibrink B, van Lier RA, van Oers MH. Immune activation modulates hematopoiesis via interactions between CD27 and CD70. Nature Immunology 2005; 6(4):412-8.

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):507-17.

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):887-92.

Mebius RE, Nolte MA, Kraal G. Development and Function of the Splenic Marginal Zone. Critical Reviews in Immunology 2004; 24(6):449-64.

Arens R#, Nolte MA#, Tesselaar K, Heemskerk B, Reedquist KA, van Lier RA, van Oers MH. Signaling through CD70 Induces B cell activation and inhibits differentiation into IgG-secreting Plasma Cells. Journal of Immunology 2004; 173(6):3901-8. (# Equally contributed)

Nolte MA, Kraal G, Mebius RE. Effects of fluorescent and non-fluorescent tracing methods on lymphocyte migration in vivo. Cytometry 2004; 61A(1):35-44.

Kater AP, Remmerswaal EB, Nolte MA, Eldering E, van Oers MH, van Lier RA. Autologous cytomegalovirus-specific T cells as effector cells in immuno-therapy of B cell chronic lymphocytic leukaemia. British Journal of Haematology 2004; 126(4):512-6.

Arens R, Schepers K, Nolte MA, van Oosterwijk MF, van Lier RA, Schumacher TN, van Oers MH. Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. Journal of Experimental Medicine 2004; 199(11):1595-1605.

Nolte MA, Arens R, Kraus M, van Oers MH, Kraal G, van Lier RA, Mebius RE. B cells are crucial for both development and maintenance of the splenic marginal zone. Journal of Immunology 2004; 172(6):3620-7.

Nolte MA
, Beliën JA, Schadee-Eestermans I, Jansen W, Unger WW, van Rooijen N, Kraal G, Mebius RE. A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp. Journal of Experimental Medicine 2003; 198:505-12.

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; 106:299-307.

Geijtenbeek TB, Groot PC, Nolte MA, van Vliet SJ, Gangaram-Panday ST, van Duijnhoven GC, Kraal G, van Oosterhout AJ, van Kooyk Y. Marginal zone macrophages express a murine homologue of DCSIGN that captures blood-born antigens in vivo. Blood 2002; 100(8):2908-16.

De Jonge WJ, Kwikkers KL, te Velde AA, van Deventer SJ, Nolte MA, Mebius RE, Ruijter JM, Lamers MC, Lamers WH. Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice. Journal of Clinical Investigation 2002; 110(10):1539-48.

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. European Journal of Immunology 2000; 30(2):626-34.

Elisen MG, van Kooij RJ, Nolte MA, Marquart JA, Lock TM, Bouma BN, Meijers JC. Protein C inhibitor may modulate human sperm-oocyte interactions. Biology of Reproduction 1998; 58(3):670-7.