CYTOTOXICITY OF T-CELLS FOR CEREBRAL ENDOTHELIUM IN MULTIPLE-SCLEROSIS

We investigated the cytotoxic effect of peripheral blood T cells on ce rebral endothelium in patients with MS. We examined in vitro the damag e to Cr-51-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 a cute relapsing MS during an exacerbation at every target-effector cell ratio tested compared with controls (P < 0.001). The percentage of en dothelial targets lysed was not significantly increased by incubation with T cells from patients with acute relapsing MS in remission and ch ronic progressive MS, compared with that of normal subjects. Relapsing MS patients during an exacerbation had significantly higher interleuk in-1 (IL-1)-alpha concentrations in cultures of targets with effector cells than normal subjects (P < 0.02). Experiments of major histocompa tibility complex (MHC)-restricted cytotoxicity in MS demonstrated inco mplete 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 init iation of immune response in acute relapsing MS during an exacerbation which appears to cause an increase in blood-brain barrier (BBB) perme ability.