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- bra in 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 n ormal and inflamed cerebral endothelial cells. The importance of relat ionship between cell surface adhesion and cytotoxic T lymphocyte (CTL) was examined by monoclonal antibodies (mAb) against adhesion receptor s. The adhesion of encephalitogenic T cells to inflamed endothelial ce lls was significantly increased as compared with normal endothelial ce lls (P < 0.00 1). The percentage lysis of inflamed endothelial target cells was significantly increased by incubation with MBP-encephalitoge nic T cell lines in the presence of MBP as compared with those of norm al endothelial targets (P < 0.0001). Intercellular adhesion molecule-1 (ICAM-1) is not involved in T cell adhesion to endothelial cells or c ytotoxic endothelial cell lysis. Antibodies against human a 4 integrin (HP 2/1) and beta 1 (A11B2) inhibited T cell adhesion, but did not bl ock cytotoxic endothelial cell lysis. These results indicate that T ce ll 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 c entral nervous system(CNS).