Survivin regulates G1 phase dependent activation-induced death in Jurkat T cells

Abstract

Peripheral T cell tolerance after negative selection of self-reactive T cells and deletion of hyperactivated T cells following the immune response occur through an apoptosis termed activation-induced cell death (AICD). The susceptibility to AICD is controlled by the cell cycle, and the cells in Gl phase are sensitive to AICD. We have investigated the molecular mechanism of cell cycle-mediated AICD and the expression of Survivin, an inhibitor of apoptosis protein (IAP) family. The mRNA analysis of Survivin showed that the expression of Survivin was decreased after AICD induction. The activity of caspase-3 was highly upregulated in G1 phase after AICD induction. No Survivin mRNA was observed in G1 phase, whereas the high level of Survivin was expressed in G2/M phase. Overexpression of Survivin by a Survivin cDNA vector, blocked the G1 phase-dependent AICD. In contrast, the loss of function of Survivin by dominant-negative vector, sensitized T cells to AICD. These results suggest that. Survivin presumably regulates the G1 phase-dependent AICD in Jurkat T cells.