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

Fas is a relative of the tumor necrosis factor receptor super-family. The receptors 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, Fas/Fas ligand interactions control cell-mediated cytotoxicity, activation-induced cell death and could confer immune privilege. In the thymus, it may regulate apoptosis during negative selection in a thymocyte subset. Autoimmune diseases are often associated with deregulated Fas expression through different mechanisms: genetic defects, Fas-mediated cytotoxicity or up-regulation of expression as a result of lymphocyte activation. Thus, in both the peripheral and central compartments, the Fas system controls the balance between lymphocyte life and death and failure to keep this balance may contribute to autoimmune disease.