ADHESION AND CYTOTOXICITY OF MYELIN BASIC PROTEIN-SPECIFIC ENCEPHALITOGENIC T-CELLS TO NORMAL AND INFLAMED CEREBRAL ENDOTHELIAL-CELLS

To study the mechanisms involved in the pathogenesis of the blood- brain barrier (BBB) breakdown in autoimmune demyelinating diseases, such as experimental allergic encephalomyelitis (EAE), we investigated the cell interaction in vitro between myelin basic protein (MBP)- specific encephalitogenic T cells and normal and inflamed cerebral endothelial cells, and the cytotoxic effect of antigen specific T cell lines on normal and inflamed cerebral endothelial cells. The importance of relationship between cell surface adhesion and cytotoxic T lymphocyte (CTL) was examined by monoclonal antibodies (mAb) against adhesion receptors. The adhesion of encephalitogenic T cells to inflamed endothelial cells was significantly increased as compared with normal endothelial cells (P < 0.00 1). The percentage lysis of inflamed endothelial target cells was significantly increased by incubation with MBP-encephalitogenic T cell lines in the presence of MBP as compared with those of normal endothelial targets (P < 0.0001). Intercellular adhesion molecule-1 (ICAM-1) is not involved in T cell adhesion to endothelial cells or cytotoxic endothelial cell lysis. Antibodies against human a 4 integrin (HP 2/1) and beta 1 (A11B2) inhibited T cell adhesion, but did not block cytotoxic endothelial cell lysis. These results indicate that T cell adhesion to inflamed cerebral endothelial cells and cytotoxicity of T cells for cerebral endothelial cells may play a central role in the breakdown of the BBB and development of inflammatory lesions in the central nervous system(CNS).