TRAF6 and T cell tolerance

TL;DRAbstract

Peripheral tolerance in CD4+ T cells is maintained by several mechanisms including suppression by CD4+CD25+ regulatory T cells, functional inactivation or anergy, and deletion. However, the molecular pathways associated with peripheral tolerance are not well understood. TRAF6 is an important signaling adaptor downstream from both TNF receptor and interleukin-1 receptor/Toll-like receptor superfamilies, thereby acting as a central regulator of APC function and innate immune response. Unexpectedly, T cell specific deletion of TRAF6 results in progressive lymphoproliferative disease characterized by multiorgan infiltration and the accumulation of activated, effector/memory CD4+ T cells. TRAF6 -/- T cells exhibit hyperactivation of the Akt pathway compared with wild-type T cells, and are resistant to both suppression by CD4+CD25+ regulatory T cells and anergy induction. These data suggest that the presence of a responder T cell intrinsic control mechanism is required to maintain peripheral

Chat with Paper

AI Agents for this Paper