Cutting edge: contributions of apoptosis and anergy to systemic T cell tolerance

Multiple pathways can induce and maintain peripheral T cell tolerance. The goal of this study was to define the contributions of apoptosis and anergy to the maintenance of self-tolerance to a systemic Ag. Upon transfer into mice expressing OVA systemically, OVA-specific DO11 CD4+ T cells are activated transiently, cease responding, and die. Bim is the essential apoptosis-inducing trigger and apoptosis proceeds despite increased expression of Bcl-2 and Bcl-x. However, preventing apoptosis by eliminating Bim does not restore proliferation or cytokine production by DO11 cells. While Foxp3 is transiently induced, anergy is not associated with the stable development of regulatory T cells. Thus, apoptosis is dispensable for tolerance to a systemic self-Ag and cell-intrinsic anergy is sufficient to tolerize T cells.