Fas/APO-1/CD95 in health and autoimmune disease: thymic and peripheral aspects

Fas is a relative of the tumor necrosis factor receptor superfamily. The re ceptors of this family play an important role in decisions of survival and cell death by apoptosis. It has become clear that Fas has multiple roles in the regulation of the immune response. In the peripheral immune system, Fa s/Fas ligand interactions control cell-mediated cytotoxicity, activation-in duced cell death and could confer immune privilege. In the thymus, it may r egulate apoptosis during negative selection in a thymocyte subset. Autoimmu ne diseases are often associated with deregulated Fas expression through di fferent mechanisms: genetic defects, Fas-mediated cytoxicity or up-regulati on of expression as a result of lymphocyte activation. Thus, in both the pe ripheral and central compartments, the Fas system controls the balance betw een lymphocyte life and death and failure to keep this balance may contribu te to autoimmune disease.