The studies proposed in this grant will examine the early steps in the pathogenesis of T-lymphocyte mediated central nervous system (CNS) immune reactions in the rat. Three areas will be studied in depth. These are: 1) The expansion of encephalitogenic cells in lymphoid tissue without the use of adjuvant. 2) Investigation of T-lymphocyte features (antigen specificity and MHC molecule expression) governing entry of T-cells to the CNS. And 3) Identification of the antigen presenting cell in the rat central nervous system. These studies will make extensive use of long- term T-cell lines and clones, immunohistochemistry, and bone marrow chimeras between rats susceptible and resistant to experimental allergic encephalomyelitis (EAE). The major scientific questions addressed by this series of experiments concern T-lymphocyte traffic in the nervous system. early features occurring following lymphocyte entry into the CNS. induction of MHC restriction molecules in the nervous system, and definition of a cell type or types with antigen presenting capabilities. This work should have direct relevance to central nervous system immunology in general and the human disease Multiple Sclerosis in particular.
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