Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation

RECEPTOR crosslinking of T-cell hybridomas induces cell activation followed by apoptosis^1-6. This activation-induced cell death requires de novo synthesis of RNA and proteins^1-3, but the actual gene products that provide the death signal have not been identified^4-6. We show here that receptor crosslinking induces Fas ligand and upregulates Fas, and that the ensuing engagement of Fas by Fas ligand activates the cell-death programme. Cell death, but not activation, can be selectively prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas ligand are the death-gene products, and their interaction accounts for the molecular mechanism of activation-induced T-cell death.