ultiple sclerosis (MS) is the most common disease of the CNS that causes prolonged and severe disability in young adults in North America and Europe. Despite intensive research efforts, the etiology and pathogenesis of MS remain to be clarified. The hypothesis that MS is an autoimmune disease is based on the following observations: (1) typical MS lesions have inflammatory plaques in the white matter containing infiltrating lymphocytes and monocytes; (2) the disease is associated with genes relevant to the immune response, especially genes of the human major histocompatibility complex (MHC) HLA region; and (3) disease activity responds to immunosuppressive and immunomodulatory treatments, such as steroids, azathioprine and interferon  (IFN-). An animal model for MS, experimental autoimmune encephalomyelitis (EAE), can be induced by immunization with myelin antigens or by adoptive transfer of myelin-specific T cells. Although MS is considered a T-cell-mediated autoimmune disease (Fig. ), autoantibodies augmenting the demyelination process in animals and intrathecal immunoglobulin G production in MS patients indicate an aberrant humoral immune response in MS.
CD95-CD95 ligand in T-cellmediated immune processes
CD95 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily and is expressed in various cell types, including CD45RO ϩ memory or previously activated T cells. CD95 transmits an apoptotic signal in susceptible target cells when induced to trimerize by ligation of agonistic antibody or the natural CD95 ligand (CD95L), a member of the TNF superfamily. The killing cascade involves the formation of a specific death-inducing signaling complex (DISC), which triggers the sequential activation of caspases. In addition to perforin-dependent lysis, CD95-mediated apoptosis is the second best characterized killing pathway used by cytotoxic T lymphocytes (CTLs), which 29