IL-15 inhibits caspase-3-mediated T cell apoptosis (47.9)

Abstract

Abstract Active caspase-3 is an effector cysteine protease crucial for apoptosis. T lymphocyte survival impinges on the ability of the cell to keep the levels of active caspase-3 in check. Previous studies have shown that despite IL-2 and IL-15 sharing γc and IL-2Rβ (CD122) receptor subunits and being capable of stimulating proliferation and activation of T cells, these cytokines differentially regulate the survival of T cells. Although IL-2 plays a crucial role in activation-induced cell death (AICD) of peripheral T cells whereas IL-15 extends survival of T cells by inhibiting AICD, the mechanism behind this difference in susceptibility to AICD is not well understood. In this study, we report that IL-2-cultured primary murine T cells manifest considerably higher levels of active caspase-3 compared to IL-15-cultured T cells. This was independent of initiator caspases, such as caspase-8 and -9. Furthermore, there was a very robust increase in caspase activity as well as cell death following α-CD3 restimulation of IL-2-cultured T cells, whereas the IL-15-cultured T cells manifested almost no increase in caspase activity or cell death. Taken together these data support the hypothesis that IL-15 can inhibit T cell apoptosis and therefore prolong T cell survival by maintaining low levels of active caspase-3.