Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis

Activation-induced cell death (AICD) of lymphocytes is an important mechamism of self-tolerance. In CD4(+) T cells, AICD is mediated by the Fas pathway and is enhanced by IL-2. To define the mechanisms of this pro-apoptotic action of IL-2, we analyzed CD4(+) T cells from wild-type and IL-2(-/-) mice expressing a transgenic T cell receptor. T cells become sensitive to AICD after activation by antigen and IL-2. IL-2 increases transcription and surface expression of Fas ligand (FasL) and suppresses transcription and expression of FLIP, the inhibitor of apoptosis. The ability of IL-2 to enhance expression of a pro-apoptotic molecule, Fast, and to suppress an inhibitor of Fas signaling, FLIP, likely accounts for the role of this cytokine in potentiating T cell apoptosis.