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.

Intriguingly, the chronic CNS inflammatory disease induced by a single LCMV infection was enhanced by second infection with a virus other than LCMV. Infection of naive transgenic mice with a virus not encoding LCMV gene products did not lead to CNS autoimmune disease. Exacerbation of CNS disease after infection with an unrelated virus required the presence of self-reactive (LCMV transgene-specific) memory lymphocytes established by a prior infection with LCMV. Studies of MBP-specific TCR transgenic mice showed that mice housed in a nonsterile environment spontaneously developed experimental allergic encephalomyelitis (48) . These observations suggested that both the TCR repertoire and exposure to environmental agents influenced susceptibility to CNS autoimmune disease. The results from our model indicate that the potential of the TCR repertoire to respond to a self-antigen, as well as the history of viral infections, are both crucial to the development of autoimmune disease.