An absolute requirement for Fyn in T cell receptor-induced caspase activation and apoptosis

The mechanisms by which caspases are stimulated following T cell receptor e ngagement are presently unknown. We show here that TCR cross-linking induce s caspase activation, annexin V binding, loss of cell viability, Fyn cleava ge, and apoptosis in a T cell hybridoma. All these events are increased in T cells overexpressing wild-type Fyn and are inhibited in cells expressing a kinase dead mutant or a soluble form of Fyn. Moreover, DNA fragmentation mediated by various proapoptotic stimuli and anti-CD3-induced caspase activ ation and DNA fragmentation are reduced significantly in mouse embryo fibro blasts and thymocytes from Fyn knockout mice respectively. These results in dicate that an active and membrane-anchored Fyn is required for T cell rece ptor-induced caspase activation and apoptosis in T lymphocytes and point ou t a specific role of Fyn in caspase activation and apoptosis in T cells.