Experiments were conducted to discern differences between encephalitogenic and non-encephalitogenic myelin basic protein (MBP)-responsive helper T cells. These cells comprise cell lines which were demonstrated to passively transfer experimental allergic encephalomyelitis (EAE) in naive mice. Cells from an encephalitogenic T cell line were plated atop monolayers consisting of syngeneic cerebrovascular endothelial cells (EC) which were untreated or treated with tumor necrosis factor-alpha (TNFalpha). Nonadherent T cells removed from the TNFalpha-treated EC culture monolayer failed to transfer EAE, whereas, those nonadherent to untreated EC culture monolayers exhibited enhanced ability to passively transfer EAE. These findings suggest that discrimination between EAE- inducing and non-encephalitogenic MBP-reactive helper T cells occurs at the level of adhesion to EC which constitute the blood-brain barrier (BBB). These findings have important implications regarding pathogenic mechanisms of adoptively transferred EAE and the role of adhesion to cerebrovascular EC in this animal model for the human autoimmune disorder, multiple sclerosis. Experiments were also conducted to characterize the infectibility and role (i.e., antigen-presenting function) of cerebrovascular EC in immune responses to murine viruses (i.e., Theiler's murine encephalo-myelitis virus and vaccinia virus). The data indicated that although EC cultures did not function as targets for cytolysis by Theiler's murine encephalomyelitis virus-immune spleen cells, they were able to do so for cytotoxic T cells from vaccinia virus-immune mice. Similar findings were obtained with regard to the capacity of EC to function as antigen- presenting cells. The data indicate cerebrovascular EC cultures are a valuable resource for the study of biology and immune response to murine viruses, such as Theiler's virus.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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