A combination of immunologic, virologic, and imaging studies in patients with multiple sclerosis (MS) together with experimental studies will address possible mechanisms of the etiology and pathogenesis of MS. Magnetic resonance imaging studies are designed to elucidate changes in the blood-brain barrier in correlation with natural history, and to further explore the genetic basis of MS. Immunologic studies will focus on attempts to understand intrathecal immunoglobulin (Ig) production in MS via study of the B-cell populations which produce the Ig. Studies of the idiotypic regulation of T-cell responses will be studied in both MS and in experimental allergic encephalomyelitis (EAE). The possible involvement of human retroviruses in MS will be pursued in order to isolate, identify, and characterize viral nucleic acid sequences in lymphocytes and brain of MS patients. This will entail production of virus-specific molecular probes and antigens from this virus. Possible mechanisms of herpes simplex virus-1 latency will be pursued via studies of the structure of the latent viral chromatin, comparing regions of the genome which have been shown to be inactive with those actively expressed during latency. Studies of immunologically-mediated induction of surface antigens on oligodendrocytes and other potential target cells in vitro will be coupled with studies of the role of the major histocompatibil- ity complex Class I antigens in mouse hepatitis-induced demyelination. Studies of oligodendrocyte gene regulation and development, myelination, and remyelination will be carried out using both human and animal cells in vitro and in vivo. Events modulating myelin basic protein (MBP) gene expression during development, the regulation of oligodendrocyte development and of the expression of myelin-associated biochemical properties, and the intracellular synthesis of myelin proteins and lipids will be studied. We will characterize growth factors, cyclic nucleotides and cell adhesion molecules affecting oligodendrocyte development. In vivo antibody- induced CNS demyelination will be employed to explore the effects of growth factors on remyelination.
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