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 < 0.001). 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 alpha 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).
Tsukada
N
N
Department of Health Medical Center and Neurology, Shinshu University, Matsumoto, Japan.
Matsuda
M
M
Miyagi
K
K
Yanagisawa
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001921:Brain / Q000098:blood supply; D002448:Cell Adhesion / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein