The mechanisms responsible for the production of experimental allergic encephalomyelitis (EAE), a model of autoimmune disease which is manifested by demyelination, are being examined. Current research is focused on an adoptively transferred model which is produced by the transfer of lymphocytes sensitized against myelin basic protein in syngeneic animals. Under optimal conditions, neurological dysfunction occurs; this is characterized pathologically by inflammation and primary demyelination. Many mice recover and develop chronic- relapsing disease. The mechanisms responsible for both the initial and the chronic disease are not known, but an early event is the migration of immune cells across the blood-brain barrier into the central nervous system (CNS). The subpopulation of T- lymphocytes which is responsible for the disease are Lyl+2- and react with antigen in association with class II MHC (Ia) molecules. Immunohistochemical examination of CNS endothelial cells (EC) in tissue section and the cytofluorographic studies of whole cells freshly isolated from the CNS indicate class II MHC molecules are not expressed on normal EC, but appear during the development of EAE. Immune lymph node cells with the capacity to transfer EAE produce gamma interferon which can induce the expression of Ia molecules on EC cells. These observations have led to the hypothesis that interaction between immune cells and the capillary endothelium leads to alterations of the blood-brain barrier. EC have been isolated from mice with acute disease. Some of the cells are Ia+ and can present antigen. The mechanism responsible for the induction of Ia molecules and the genetics of Ia expression is being studied in vitro in strains of mice that are susceptible and resistant to EAE.
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