The principal physiologic function of the immune system is the elimination of infectious organisms. The effector mechanisms that are responsible for protective immunity are also capable of injuring host tissues. In some situations, specific immune responses have little or no protective value, and the harmful consequences become dominant; examples include autoimmune diseases caused by pathologic immune responses against self-antigens, and infections in which the host response and not the infectious agent is the main cause of pathology. The immune system has evolved multiple, nonoverlapping mechanisms for controlling potentially harmful reactions. Failure of these mechanisms may lead to tissue injury and disease. Conversely, the same regulatory mechanisms may be exploited therapeutically, for instance, to prevent the rejection of tissue transplants. Potentially injurious immune reactions may be prevented either by functionally inactivating the responding lymphocytes or by killing the cells. The principal cytolytic mechanism involved in controlling lymphocyte responses is a tightly regulated pathway of apoptotic cell death triggered by an interaction of Fas (CD95) with its ligand. Fas is a member of the tumor necrosis factor (TNF) receptor family of cell surface proteins, and Fas ligand (FasL) is a member of the TNF family of membrane and secreted proteins. The biochemistry of these proteins and the mechanisms by which Fas triggers apoptosis have been subjects of recent reviews (