Specific resistance of T cells to CD95-induced apoptosis during S phase of the cell cycle.

We have examined the susceptibility of mouse thymocytes and Con A-activated mature T cells to CD95 (Fas; APO-1)-induced apoptosis at different phases of the cell cycle. Signaling through CD95, induced by murine CD95 ligand expressed on fibroblasts, resulted in the preferential apoptosis of T cells in G0-G1 phase of the cell cycle. T cells in S phase were selectively protected. CD95-induced apoptosis was inhibited by exogenous IL-2, which increases the percentage of cells in S phase. The inverse relationship between DNA synthesis and apoptosis in CD95-ligated T cells was not observed during the spontaneous death of T cells in culture or during propriocidal apoptosis due to TCR cross-linking, to which cells in S phase were susceptible. These results show that in T cells there is no distinctively apoptosis-vulnerable phase of the cell cycle; instead, apoptosis can occur at different phases of the cycle depending on the apoptotic stimulus.