Current research is focused on a chronic-relapsing model of experimental allergic encephalomyelitis (EAE). This disease is produced by the transfer of lymphocytes sensitized against MBP to syngeneic mice. The neurologic dysfunction is characterized pathologically by inflammation and primary demyelination. The immunological mechanisms responsible for the initial episode and the chronic disease are being investigated. Because the migration of immune cells from the blood into the central nervous system occurs before clinical disease, interactions between endothelial cells (EC) which form the blood-brain barrier and immune cells are being studied in vitro. The function of various adhesion molecules in both adherence and lymphocyte signaling are being examined. The effects of various cytokines on lymphocyte-EC interactions and on clinical disease are being studied. Previous studies demonstrated that transforming growth factor-beta1 (TGF-beta1) temporarily reduced the clinical severity of EAE. Current studies show that long-term administration of the related compound, TGF-beta2 reduces the severity of the clinical course of the disease and decreases the inflammation and demyelination associated with EAE. Immunohistochemical studies demonstrate TGF-beta in the EAE lesion. T cells producing TGF-beta in the lesion may contribute to the relapsing nature of disease in EAE. The effect of agents known to induce TGF-beta are being studied in the EAE model. Retinoids are a class of molecules which can induce TGF-beta and which have profound effects on cell growth and differentiation. Administration of retinoids results in an improvement of the clinical course of EAE. Also, retinoids increase IL-4 and decrease IL-2, gamma interferon and tumor necrosis factor gene expression in MBP-specific T cells. These results indicate that retinoids may alter cytokine production on encephalitogenic T cells. The influence of environmental factors on autoimmune disease is also being examined. Bacterial superantigens which can cause nonantigen-specific T-cell receptor activation can produce sufficient activation of MBP-specific T cells to allow induction of disease in some mouse strains.
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