Experimental autoimmune encephalomyelitis (EAE) is a T-Lymphocyte- mediated demyelinating condition and serves as an experimental model of the human disease multiple sclerosis (MS). Previous immunocytochemical studies of acute EAE in the rat have demonstrated perivascular infiltration of immune (CD4+) cells into the central nervous system (CNS). Changes in CNS endothelium as well as blood brain barrier injury occurs in both acute and chronic relapsing EAE. From studies in inflammatory disease models we know that these changes in the endothelium, loosely termed """"""""endothelial cell activation"""""""", are often cytokine-mediated and important in leukocyte-endothelial cell interaction, and the resultant migration of leukocytes into sites of inflammation. We propose that EC activation is an important step in acute EAE induction and recovery in the Lewis rat.
In specific aim #1 and #2, we will examine cytokine and leukocyte mediated EC activation in Lewis rats. Activated EC express activation antigens on the cell surface. Expression of EC activation antigens in response to cytokines and leukocyte co-culture will be measured on intact CNS microvessels and EC primary cultures using confocal laser cytometry and immunofluorescence flow cytometry.
Specific aims #3 and #4 will examine EC expression of activation antigens and response to co-culture sequentially through induction and recovery from acute EAE. Emphasis will be placed on the potential role of CD4+ suppressor cells in recovery. In particular, we will study possible interactions of Ts with EC.
