The CD95 system and the death of a lymphocyte

Since the discovery of the CD95 receptor in 1989 and its ligand in 1993 as major initiators of apoptosis, extensive progress has been made in understanding their functions in programmed cell death. This review will summarize the cellular, molecular and biochemical requirements that play an important role in the CD95 system. Of importance in understanding the biology of CD95 are naturally occurring mutations in the mouse, the lpr and gld mutations, in which the expression of either the receptor or its ligand is disturbed. This review will discuss the roles of the CD95 receptor/ligand system in negative selection of thymocytes and in the peripheral T- and B-lymphocyte compartment. Emphasis is put on its role in cell-mediated cytotoxicity, transplant rejection and on its pathophysiological role in organ damage. Finally, recent data are presented to give an overview of CD95-associated signalling proteins.