IN-VIVO DEPLETION OF CD8-CELLS PREVENTS LESIONS OF DEMYELINATION IN SEMLIKI FOREST VIRUS-INFECTION( T)

Following intraperitoneal infection of BALB/c mice with the A7(74) str ain of Semliki Forest virus, the virus spreads to the central nervous system (CNS) and initiates an acute inflammatory reaction which includ es lesions of primary demyelination. This demyelination is dependent u pon activated T lymphocytes. To determine whether CD4+ or CD8+ T cells are involved in the pathogenesis of the demyelination, we have invest igated the course of infection in animals treated with monoclonal anti -CD4 or anti-CD8 antibodies. In the normal course of infection, virus was detectable in the brain by infectivity assay and in situ hybridiza tion for up to 14 days. Antiviral immunoglobulin M (IgM) and all subcl asses of IgG were produced. From day 10 to 21 postinfection lesions of inflammatory demyelination were present, most notably in the cerebell um and corpus callosum but also in other white matter tracts. Administ ration of anti-CD4 antibodies removed CD4+ cells from the spleen, prev ented production of antiviral IgG, increased virus titers in the brain , and increased demyelination. Administration of anti-CD8 antibodies d epleted CD8+ cells from the spleen and did not affect antiviral IgG sy nthesis or spread of brain virus but reduced CNS inflammatory response s and virtually abolished lesions of demyelination. Administration of both antibodies depleted both T-cell subsets from the spleen, prevente d IgG antibody production, increased brain virus, and abrogated both C NS inflammation and lesions of demyelination. In conclusion, the CNS d emyelination induced by Semliki Forest virus can be prevented by in vi vo depletion of CD8+ T lymphocytes.