Immunosuppression promotes CNS remyelination in chronic virus-induced demyelinating disease.
Immunosuppression using cyclophosphamide or anti-T cell monoclonal antibodies (mAbs) directed at CD4 or CD8 promoted remyelination of CNS axons in the spinal cords of mice infected chronically with Theiler's virus. Treatment with a mAb directed at class II major histocompatibility gene products did not increase the extent of CNS remyelination. Following immunosuppressive treatment, quantitative morphometry revealed a five- to sevenfold increase in new myelin synthesis. Proliferating nervous system cells were identified at the edges of remyelinated lesions by their incorporation of [3H]thymidine. CNS remyelination occurred in mice depleted of selected subsets of T lymphocytes despite the local persistence of viral antigen. These findings indicate that CNS remyelination occurs as a normal consequence of primary myelin injury, but factors associated with immune T cells somehow impair remyelination. Interference with the function of immune T cells enhances CNS remyelination by oligodendrocytes. Similar depletion of immune T cells may allow for enhanced remyelination in the CNS of patients with chronic multiple sclerosis.
Rodriguez
M
M
Department of Neurology, Mayo Medical School, Rochester, MN.
Lindsley
M D
MD
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001345:Autoradiography; D001369:Axons / Q000276:immunology / Q000502:physiology / Q000648:ultrastructure; D002455:Cell Division / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology* / Q000503:physiopathology; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D004769:Enterovirus Infections / Q000276:immunology / Q000503:physiopathology; D007165:Immunosuppression Therapy; D004680:Maus Elberfeld virus / Q000276:immunology; D051379:Mice; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D009457:Neuroglia / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000956:Antigens, Viral