FAS(CD95) FASL INTERACTIONS REQUIRED FOR PROGRAMMED CELL-DEATH AFTER T-CELL ACTIVATION

RECEPTOR crosslinking of T-cell hybridomas induces cell activation fol lowed by apoptosis(1-6). This activation-induced cell death requires d e novo synthesis of RNA and proteins(1-3), but the actual gene product s that provide the death signal have not been identified(4-6). We show here that receptor crosslinking induces Fas ligand and upregulates Fa s, and that the ensuing engagement of Fas by Fas ligand activates the cell-death programme. Cell death, but not activation, can be selective ly prevented by a soluble Fas-immunoglobulin fusion protein. Thus, Fas and Fas ligand are the death-gene products, and their interaction acc ounts for the molecular mechanism of activation-induced T-cell death.