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Neuroimmunology Unit, Montreal Neurologic Institute, and Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Oligodendrocytes and their myelin membranes are the apparent target of the autoimmune response that characterizes the human adult central nervous system-demyelinating disease multiple sclerosis. Human oligodendrocytes do not express MHC class II molecules, a requirement for MHC-restricted injury mediated by myelin-reactive CD4+ T cells, the cell type implicated in initiating the disease process. In this study we observed that human adult central nervous system-derived oligodendrocytes can be susceptible to non-MHC-restricted lysis mediated by myelin basic protein-reactive CD4+ T cell lines. Cytotoxicity was significantly greater (37 ± 4 vs 7 ± 3%) with cell lines in which a high proportion of cells (mean, 28 ± 6%) expressed CD56 compared with cytotoxicity mediated by low CD56 cell lines (8 ± 2%). High CD56 cell lines, when rested in IL-2, lost cytotoxic activity and had reduced expression of CD56 (mean, 5 ± 2%). CD4+ T cells isolated from short term (3-day) anti-CD3/IL-2-activated mononuclear cell cultures did not express CD56 and were not cytotoxic to oligodendrocytes unless lectin was added. In contrast, an enriched population of non-T cells extracted from the same activated MNC cultures expressed CD56 as well as other NK cell-associated surface molecules and was cytotoxic. These results indicate the potential susceptibility of human oligodendrocytes to non-MHC-restricted injury mediated by both Ag-reactive and nonspecific cellular immune effector cells, with CD56 expression being a common feature of the effector cells.
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