The mechanism of effector T cell formation
Next to the impact that activated T cells can have on the hematopoietic process, we also investigate the molecular mechanisms that underly the formation of effector and memory T cells. This research, which is performed in close collaboration with Prof Dr René van Lier, has its roots in a longstanding interest in the consequences of T cell co-stimulation through CD27 and its ligand CD70. Recent findings demonstrate that CD27 maintains clonally diverse CD8 T cell responses of low antigen affinity to protect against viral variants. Moreover, we also investigate the consequences of costimulation mediated through GITR and its ligand. Furthermore, we have discovered a new transcription factor, which we named HOBIT. Our data infer that HOBIT is an evolutionary conserved transcription factor that is strongly linked to a number of key features of terminally differentiated effector cells. This gives us the possibility to unravel the role of this molecule in T cell immunity.
Key publications:
- Libregts S, van Olffen RW, van der Sluijs KF, van Lier RA, Nolte MA. Function of CD27 in helper T cell differentiation. Immunol Lett 2011 Jan 26. [Epub ahead of print].
- Hertoghs KM, Moerland PD, van Stijn A, Remmerswaal EB, Yong SL, van de Berg PJ, van Ham SM, Baas F, ten Berge IJ, van Lier RA. Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. J Clin Invest 2010; 120(11):4077-90.
- Van de Berg PJ, Griffiths SJ, Yong SL, Macaulay R, Bemelman FJ, Jackson S, Henson SM, ten Berge IJ, Akbar AN, van Lier RA. Cytomegalovirus infection reduces telomere length of the circulating T cell pool. J Immunol 2010; 184(7):3417-23.
- 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 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.
- 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.
- Van Stijn A, Rowshani AT, Yong SL, Baas F, Roosnek E, ten Berge IJ, van Lier RA. Human cytomegalovirus infection induces a rapid and sustained change in the expression of NK cell receptors on CD8+ T cells. J Immunol 2008; 180(7):4550-60.
- Van Oosterwijk MF, Juwana H, Arens R, Tesselaar K, van Oers MH, Eldering E, van Lier RA. CD27-CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development. Int Immunol 2007; 19(6):713-8.
- Van Leeuwen EM, Remmerswaal EB, Heemskerk MH, ten Berge IJ, van Lier RA. Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection. Blood 2006;108(9):3121-7.
- De Bree GJ, van Leeuwen EM, Out TA, Jansen HM, Jonkers RE, van Lier RA. Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung. J Exp Med 2005; 202(10):1433-42.
- Van Leeuwen EM, de Bree GJ, Remmerswaal EB, Yong SL, Tesselaar K, ten Berge IJ, van Lier RA. IL-7 receptor alpha chain expression distinguishes functional subsets of virus-specific human CD8+ T cells. Blood 2005; 106(6):2091-8.