Induction of CD8 T cell-mediated EAE by viral infections in a CD8 TCR transgenic mouse model (130.31)

Abstract

Abstract Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Besides CD4 T cells, CD8 T cells have recently been shown to mediate the pathogenesis of EAE. The cause of MS is not clear, but infections have been suggested. In this study, we investigated the roles of viral infections in the development of EAE on a CD8 T cell receptor (TCR) transgenic mouse model. Infection with wildtype vaccinia virus broke tolerance and triggered atypical EAE in a TCR transgenic mouse specific for myelin basic protein 79–87 (MBP79-87). CD8 T cells up-regulated activation markers and trafficked to the CNS in virus-infected mice. Interestingly, CD8 T cells from TCR-transgenic MBP deficient mice also displayed activation markers, and had cytolytic effector function similar to that from TCR transgenic MBP sufficient mice. T cell activation was not due to MBP TCR cross-reactivity against vaccinia virus. Furthermore, preliminary data showed that disease induction by vaccinia virus required endogenous TCRs. Ongoing experiments are extending these observations into another viral infection. In conclusion, the results suggest that viral infection may induce EAE by activation through dual TCR.