This research proposal describes a series of experiments to be conducted during the first two years of the TIDA award which are designed to identify and quantitate the cells infiltrating the CNS after the induction of EAE under a variety of conditions. The model to be used will be the Lewis rat and the syngeneic Lewis EAE resistant rat. A sensitive immunohistological method will be used to determine the phenotype and density of infiltrating cells in order to define the infiltrates and contrast them with those of acute, active EAE. These investigations will address the problems of: cell types found in chronic lesions; the effect on cellular infiltrates produced by adjuvant variations in the inoculum; cell phenotypes found in adoptively transferred EAE; and the extent and nature of the protection afforded by active and passive immunization protocols. To perform the analyses of the manipulations requiring adoptively transferred EAE, a rat derived MBP reactive T-lymphocyte cell line(s) will be established and maintained. By these proposed studies of cell phenotypes and cell densities in the target organ, I hope to define the changes occurring among the immunologic effector cell types which are associated with passive EAE, chronic EAE and various """"""""immunized"""""""" states. This data will identify the T-cell subtypes pathogenetically active in EAE in Lewis and Lewis resistant rats. During the final years of the grant these T-cell subtypes will be cultured and individually investigated in an effort to further elucidate the basic cellular mechanisms involved in EAE production and prevention. During the first two years of the TIDA greater facility with basic cellular immunology theory and techniques will be sought. This should permit research in the third through fifth year of the award to employ the products of B and T cell hybridomas in further dissecting the mechanisms of rat EAE. Teaching and clinical practice aspects of the five years of the TIDA should remain constant and are described in detail.
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