The objective of this research proposal is to examine the role of cerebrovascular endothelia (CVE) in the pathogenesis of Theiler's virus- induced demyelination as a model of multiple sclerosis. Firstly, we intend to compare the lymphokine induced expression of major histocompatibility antigens on murine cerebrovascular endothelia, astrocytes and macrophages. Secondly, an investigation of the antigen presenting capabilities of endothelia, astrocytes and macrophages will be undertaken. The antigens in question will be Theiler's virus peptides, representing immunodominant regions of the viral polypeptides 'and hen egg lysozyme as a control antigen. Thirdly, we will determine whether antigen presentation at the CVE leads to the egress of I specific T cells across the blood:brain barrier into the central nervous system (CNS). Finally, we will study the effect of lymphokines on the rate of viral I replication in endothelia, astrocytes and oligodendrocytes. A comparison of these phenomena in strains of mice that are resistant and susceptible to Theiler's virus-induced demyelination may lead to a better understanding of the genetic basis of """"""""resistance mechanisms. These studies represent a new approach in our efforts to understand the role of infectious agents in demyelinating diseases such as multiple sclerosis and we are placing special emphasis on the CVE because we believe this aspect is crucial to the initiation and subsequent pathology of such diseases.
