Experimental allergic encephalomyelitis (EAE) is a model for the human autoimmune disease multiple sclerosis, and results from the activation of myelin-reactive CD4 T cells. The mechanisms underlying this disease model are poorly understood. Selectins play a key role in the entry of lymphocytes into lymphoid organs where priming of autoreactive T- lymphocytes takes place, and leukocytes to sites of inflammation where tissue destruction occurs in autoimmunity. We will employ selectin- deficient mice to determine the role of these molecules in EAE. Our preliminary data show that L-selectin is required for EAE to develop. We will determine the nature of the L-selectin deficiently in EAE and upon which cell populations L-selectin must be expressed for disease. We will further specificity determine whether L-selectin is required for the entry of inflammatory cells into the CNS or for the effector mechanisms of tissue destruction within the CNS. Finally, we will determine whether endothelial selectins (E/P selectins) are required for EAE, and if so, why.

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Yale University
New Haven
United States
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