Multiple sclerosis: an overview.

Demyelinating lesions of MS are infiltrated by activated T-lymphocytes and macrophages with secretion of soluble factors. This results in the synthesis of oligoclonal immunoglobulin (IgG) by plasma cells. The activated T-lymphocytes migrate from the peripheral blood to the CNS. This hyperactive state is linked to a selective loss of the suppressor/inducer T-cell subset. Administration of a soluble factor--interferon gamma--enhances the immune response by promoting class II antigen expression on macrophages or astrocytes, resulting in a relapse. However, the reason for T-cell activation in peripheral blood is not known, nor is the antigen. Myelin basic protein (MBP) has been considered to be the target since MBP is able to induce chronic relapsing allergic encephalomyelitis (CRAE) in an animal model of MS. Yet other myelin antigens have succeeded in inducing CRAE in animal models, and anti-MBP antibodies have been found in healthy individuals. The possibility that the hyperimmune state results from a viral infection has not yet been proven. It is known that in Caucasians, a genetic susceptibility factor is linked to class II MHC. Using MRI it has been found that the presence of new plaques was not regularly correlated with relapses, which indicates that MS is an ongoing pathology process. Most drugs used in MS influence the immune response but have potential toxicity. Monoclonal antibodies offer the opportunity of specific targeting of T-cells and are promising for the future.