Role of th1 and th2 responses to individual epitopes of theiler's virus during the course of demyelination

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. T cells play an important role in this immune-mediated disease. We have previously identified two major T cell epitopes within the VP1 (VP1233.250) and VP3 (VP32t37) capsid proteins, based on the reactivities of T cell clones derived from demyelinating spinal cords of virus-infected SJL/J mice. Together with the previously identified VP2 (VP27t) epitope, these three T cell epitopes account for the majority of MHC class ll-restricted T cell responses to TMEV. T cells responsive to the individual epitopes appeared at similar time points during the course of TMEV-induced demyelination. However, peptide-priming experiments indicate that immunization with VP1 and VP2, but not VP3, accelerates the pathogenesis. Further cytokine profiles of T cells from virus-infected mice upon stimulation with individual epitope-peptides in vitro indicate that VP1 and VP2 peptides elicit Th1 cytokines whereas VP3 induces only Th2 cytokines. In contrast, a low-pathogenic variant virus containing a single amino acid substitution in the VP1 epitope resulted in Th2 response. These results strongly suggest that the Th1-type T cells specific for VP1 and VP2 are involved in the pathogenesis of viral demyelination induced by TMEV.