NON-MHC-RESTRICTED CELL-MEDIATED LYSIS OF HUMAN OLIGODENDROCYTES IN-VITRO - RELATION WITH CD56 EXPRESSION

Oligodendrocytes and their myelin membranes are the apparent target of the autoimmune response that characterizes the human adult central ne rvous system-demyelinating disease multiple sclerosis, Human oligodend rocytes do not express MHC class II molecules, a requirement for MHC-r estricted injury mediated by myelin-reactive CD4(+) T cells, the cell type implicated in initiating the disease process. In this study we ob served that human adult central nervous system-derived oligodendrocyte s can be susceptible to non-MHC-restricted lysis mediated by myelin ba sic protein-reactive CD4(+) T cell lines. Cytotoxicity was significant ly greater (37 +/- 4 vs 7 +/- 3%) with cell lines in which a high prop ortion of cells (mean, 28 +/- 6%) expressed CD56 compared with cytotox icity mediated by low CD56 cell lines (8 +/- 2%). High CD56 cell lines , when rested in IL-2, lost cytotoxic activity and had reduced express ion of CD56 (mean, 5 +/- 2%). CD4(+) T cells isolated from short term (3-day) anti CD3/IL-2-activated mononuclear cell cultures did not expr ess CD56 and were not cytotoxic to oligodendrocytes unless lectin was added, In contrast, an enriched population of non-T cells extracted fr om the same activated MNC cultures expressed CD56 as well as other NK cell-associated surface molecules and was cytotoxic, These results ind icate the potential susceptibility of human oligodendrocytes to non-MH C-restricted injury mediated by both Ag-reactive and nonspecific cellu lar immune effector cells, with CD56 expression being a common feature of the effector cells.