Cytotoxicity of T cells for cerebral endothelium in multiple sclerosis

• Published in: Journal of the neurological sciences Vol. 117; no. 1; pp. 140 - 147
• Main Authors: Tsukada, Naoyuki, Matsuda, Masayuki, Miyagi, Koichi, Yanagisawa, Nobuo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.07.1993; Elsevier Science
• Subjects: Adolescent; Adult; Aged; Animal cells; Antibodies, Monoclonal - immunology; Biological and medical sciences; Blood-Brain Barrier; Brain - immunology; Cell cultures. Hybridization. Fusion; Cell Line; Cytotoxic T cell; Cytotoxicity, Immunologic; Endothelial cell; Endothelium - immunology; Female; Fundamental and applied biological sciences. Psychology; HLA Antigens - immunology; Humans; Infant; Infection - immunology; Interleukin-1 - biosynthesis; Isotope release; Major histocompatibility complex (MHC); Male; Middle Aged; Molecular and cellular biology; Multiple sclerosis; Multiple Sclerosis - classification; Multiple Sclerosis - immunology; Nervous System Diseases - immunology; T-Lymphocytes, Cytotoxic - immunology; Target-effector cell ratio; Target-effector cell ratio; Endothelial cell; Multiple sclerosis; Major histocompatibility complex (MHC); Cytotoxic T cell; Isotope release; Human; Cell culture; Nervous system diseases; T-Lymphocyte; Cytotoxicity; Exploration; Blood; Inflammatory disease; Brain (vertebrata)
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(93)90166-V

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)-α 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.