Pathogenesis of virus-induced immune-mediated demyelination

Theiler's murine encephalomyelitis virus-induced demyelinating disease has been extensively studied as an attractive infectious model for human multip le sclerosis. Virus-specific inflammatory Th1 cell responses followed by au toimmune responses to myelin antigens play a crucial role in the pathogenic processes leading to demyelination. Antibody and cytotoxic T cells (CTL) r esponses to virus appears to be primarily protective from demyelinating dis ease. Although the role of Th1 and CTL responses in the induction of demyel inating disease is controversial, assessment of cytokines produced locally in the central nervous system (CNS) during the course of disease and the ef fects of altered inflammatory cytokine levels strongly support the importan ce of Th1 responses in this virus-induced demyelinating disease. Induction of various chemokines and cytokines in different glial and antigen presenti ng cells upon viral infection appears to be an important initiation mechani sm for inflammatory Th1 responses in the CNS. Coupled with the initial infl ammatory responses, viral persistence in the CNS may be a critical factor f or sustaining inflammatory responses and consequent immune-mediated demyeli nating disease.