Cleavage of anti-apoptotic Bcl-2 family members after TCR stimulation contributes to the decision between T cell activation and apoptosis.

Engagement of the TCR induces activation-induced cell death (AICD) of T cells that have been previously stimulated. However, a portion of these T cells can survive and undergo further activation. The molecular mechanism that decides whether a T cell will live or die after TCR re-engagement is unclear. We found that cross-linking of TCR in preactivated primary mouse T cells led to the cleavage of anti-apoptotic Bcl-2 and Bcl-xL in dying cells. Cleavage-resistant Bcl-2 and Bcl-xL were more efficient than their wild-type counterparts in the inhibition of apoptosis in primary mouse T cells and in the H9 T cell line after TCR cross-linking. In contrast, the surviving T cells after TCR re-engagement displayed upregulation of Bcl-xL, and knockdown of Bcl-xL promoted AICD. This indicates that caspase-mediated cleavage of anti-apoptotic Bcl-2 or Bcl-xL facilitates AICD in T cells, whereas upregulation of Bcl-xL promotes T cell survival and allows further T cell activation. Our data suggest that cleavage of anti-apoptotic Bcl-2 and Bcl-xL contributes to the decision between T cell activation and apoptosis after TCR re-engagement.