Cytotoxicity of T cells for cerebral endothelium in multiple sclerosis.
We investigated the cytotoxic effect of peripheral blood T cells on cerebral endothelium in patients with MS. We examined in vitro the damage to 51Cr-labelled dissociated human brain endothelial cells produced by mitogen-stimulated T cell lines from patients with MS and controls. Endothelial targets were lysed by T-lymphocytes from patients with acute relapsing MS during an exacerbation at every target-effector cell ratio tested compared with controls (P < 0.001). The percentage of endothelial targets lysed was not significantly increased by incubation with T cells from patients with acute relapsing MS in remission and chronic progressive MS, compared with that of normal subjects. Relapsing MS patients during an exacerbation had significantly higher interleukin-1 (IL-1)-alpha concentrations in cultures of targets with effector cells than normal subjects (P < 0.02). Experiments of major histocompatibility complex (MHC)-restricted cytotoxicity in MS demonstrated incomplete blocking of specific lysis by either anti-MHC class I or class II monoclonal antibody (mAb). These results indicate that cytotoxicity of T cells for cerebral endothelial cells may play a role in the initiation of immune response in acute relapsing MS during an exacerbation which appears to cause an increase in blood-brain barrier (BBB) permeability.
Tsukada
N
N
Department of Medicine (Neurology), Shinshu University, School of Medicine, Matsumoto, Japan.
Matsuda
M
M
Miyagi
K
K
Yanagisawa
N
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D001812:Blood-Brain Barrier; D001921:Brain / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004727:Endothelium / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D007239:Infections / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000145:classification / Q000276:immunology*; D009422:Nervous System Diseases / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D007375:Interleukin-1