Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

Evans, Claire F.; Horwitz, Marc S.; Hobbs, Monte V.; Oldstone, Michael B.A.

Primary infection of transgenic mice with LCMV led to CNS infiltration by CD8 ϩ and CD4 ϩ T cells, at a ratio of ‫.1:5ف‬ This was not surprising, because the primary T cell response to LCMV is mediated by CD8 ϩ cells (13, 14) . However, no obvious damage to oligodendrocytes was observed after a single LCMV infection of transgenic mice. After a second viral infection of the transgenic mice, the proportion of CD4 ϩ T cells increased relative to the number of CD8 ϩ T cells (CD8 ϩ /CD4 ϩ , 2:1). Focal areas of myelin degradation were observed (Fig. 4) , and expression of both MHC class I and class II molecules was found on oligodendrocytes (Horwitz, M.S., C.F. Evans, and M.B.A. Oldstone, manuscript submitted for publication). These findings suggest that CD8 ϩ and/or CD4 ϩ T cells may interact directly with oligodendrocytes and play a role in oligodendrocyte injury. In addition, the total number of infiltrating T cells in the CNS increased three-to fivefold after a second infection with LCMV. Other models of autoimmune diseases have shown that the number of self-reactive T cells influences the development of disease (44) (45) (46) , so it is possible that the myelin damage seen after a second LCMV in-fection was a result of the increased numbers of infiltrating T cells.