CD8-decient SJL mice display enhanced susceptibility to Theiler’s virus infection and increased demyelinating pathology

Theiler’s murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressivedemyelinating disease in susceptiblemouse strains characterized by inammatory mononuclear inŽltrates and spastic hind limb paralysis. Our lab has previouslydemonstrated a critical role for TMEVand myelin-speciŽc CD4+ T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8+ T cells to the TMEVinduced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that ̄2M-deŽcient SJL mice have similar disease incidence rates to wild-type controls, however ̄2M-deŽcient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV andmyelin proteolipid (PLP) epitopes, and signiŽcantly higher levels of CNS demyelination and macrophage inŽltration at 50 days post-infection. ̄2M-deŽcient mice also displayed a signiŽcant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8+ T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4+ T cells in this capacity and further emphasize the potential for CD8+ T cells to contribute to protection from TMEV-induced demyelination. Journal of NeuroVirology (2001) 7, 409–420.