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

Theiler's murine encephalomyelitis virus (TMEV) infection of the central ne rvous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltr ates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV and myelin-specific CD4(+) T cells in initiating an d perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infecti on and persistence. For this reason, we investigated the contribution of CD 8(+) T cells to the TMEV induced demyelinating pathology in the highly susc eptible SJL/J mouse strain. Here we show that beta 2M-deficient SJL mice ha ve similar disease incidence rates to wild-type controls, however beta 2M-d eficient mice demonstrated earlier onset of clinical disease, elevated in v itro responses to TMEV and myelin proteolipid (PLP) epitopes, and significa ntly higher levels of CNS demyelination and macrophage infiltration at 50 d ays post-infection. beta 2M-deficient mice also displayed a significant ele vation in persisting viral titers, as well as an increase in macrophage-der ived pro-inflammatory cytokine mRNA expression in the spinal cord at this s ame time point. Taken together, these results indicate that CD8(+) T cells are not required for clinical or histologic disease initiation or progressi on in TMEV-infected SJL mice. Rather, these data stress the critical role o f CD4(+) T cells in this capacity and further emphasize the potential for C D8(+) T cells to contribute to protection from TMEV-induced demyelination.