Caspase activation is required for T cell proliferation

Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death vi a recruitment of the adaptor protein Fas-associated death domain (FADD), re sulting in activation of a caspase cascade. It was thus surprising that T l ymphocytes deficient in FADD were reported recently to be not only resistan t to Fast-mediated apoptosis, but also defective in their proliferative cap acity. This finding suggested potentially dual roles of cell. growth and de ath for Fas and possibly other death receptors. We report here that CD3-ind uced proliferation and interleukin 2 production by human T cells are blocke d by inhibitors of caspase activity. This is paralleled by rapid cleavage o f caspase-8 after CD3 stimulation, but no detectable processing of caspase- 3 during the same interval. The caspase contribution to T cell activation m ay occur via TCR-mediated upregulation of Fast, as Fas-Fc blocked T cell pr oliferation, whereas soluble FasL augmented CD3-induced proliferation. Thes e findings extend the role of death receptors to the promotion of T cell gr owth in a caspase-dependent manner.