A role for TRAF5 in CD8+ T cell responses.

Effective clearance of and immunity to intracellular pathogens depends on activation of T lymphocytes and generation of effective antigen specific memory. The quality and magnitude of T cell memory is modulated by costimulation. TNFR family members CD27, OX40 and GITR are integral to T cell function and are expressed at different stages in T cell activation. These molecules interact with TRAF5, an adaptor molecule that translates signals from these receptors into modulation of gene transcription and kinase activation. However, the significance of TRAF5 in T cell immunity in vivo remains unclear. We hypothesize that TRAF5 is a key mediator of signaling through these receptors and the absence of this molecule will result in defects in T cell expansion due to decreased survival. Infection of mice deficient in TRAF5 with L. monocytogenes resulted in significantly fewer antigen‐specific CD8+ T cells during the primary and secondary response. Memory levels of CD8+ T cells were also reduced. Our results show that this defect is not due to defects in APC function and is T cell intrinsic in nature. Preliminary results suggest that CD8+ T cells from TRAF5 deficient mice are more susceptible to apoptosis following activation.