ABSTRACT
I. OVERVIEW OF MULTIPLE SCLEROSIS Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), which has been postulated to be a T-cell-mediated autoimmune disease (1). Although the etiology of MS is unknown, most investigators believe that the immune system is intimately involved in the progression of the disease (2). MS is clinically associated with periods of disability (relapse) alternating with periods of recovery (remission) but often leading to progressive neurological disability (3). The lesions in the CNS are similar to the lesions produced by T-lymphocyte delayed-type (DTH) hypersensitivity reactions. Studies of the cellular immune system in tissue compartments have suggested that there is a sequestration of antigen-specific T-cell populations in the cerebrospinal fluid (CSF) (4). A major hypothesis concerning the CNS inflammation is that T lymphocytes are reacting to an (un)identified self-antigen(s) intrinsic to myelin (such as myelin basic protein [MBP] or proteolipid protein [PLP]), and these T lymphocytes damage myelin directly or by activating macrophages and other agents of inflammation. Progression or recurrence of immune damage appears to result from a failure of normal regulatory mechanisms to suppress the immune process in MS (5). We have recently shown that there is a CD3 pathway defect (6) and that secretion of interferon-y (IFNy) was significantly decreased and transforming growth factor-f3 (TGF-p)
Brod
was significantly increased via anti-CD3 mAb in stable relapsing-remitting MS (RRMS) patients compared with controls (7).
