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.

For an autoimmune T cell response to occur, self-reactive T cells must escape thymic negative selection as well as peripheral tolerance by clonal deletion or induction of anergy. In this model, no evidence for T cell tolerance to the viral (self) transgene products was obtained. Thymic ex-pression of transgene mRNA was not detected by RT-PCR, and CTL and antibody responses to the transgene were similar to those observed in nontransgenic mice. Since transgene product-specific CTL could be isolated from the brains of transgenic mice following infection with LCMV, this indicated that self-reactive T cells in the periphery were activated by the viral infection and trafficked into the CNS where the transgene was expressed. T cells reactive to MBP have been isolated from healthy individuals as well as MS patients (35) . Therefore, it is possible that infection by a virus sharing epitopes with a myelin component such as MBP could result in activation of self-reactive T cells that would cross the blood-brain barrier and recognize oligodendrocytes presenting self-peptides.