Using immunohistochemical techniques, we examined major histocompatibility complex (MHC) antigen expression on astrocytes, oligodendrocytes, and macrophages-microglia derived from surgically resected tissue from young adults and maintained in dissociated cell cultures supplemented with either fetal calf or human AB serum. The majority of these cells in culture expressed class I MHC antigens. MHC class II expression was observed on only a restricted proportion of astrocytes either under basal or induction conditions (gamma-interferon, activated lymphocyte supernatants), on the majority of macrophages-microglia under inducing conditions, and not on oligodendrocytes. MHC class II expression on astrocytes in culture did not correlate with the extent of in situ gliosis or with in vitro cell morphology. MHC antigen expression was not detected in situ immunohistochemically. These data extend observations on the dissociation of in vivo and in vitro expression of MHC antigens on glial cells. The apparent greater expression of MHC class II antigens on macrophages-microglia compared to astrocytes raises the issue of the relative roles of each of these cell types in promoting immune reactivity under pathologic conditions.

The majority of human oligodendrocytes in enriched glial cell cultures expresses class I major histocompatibility complex (MHC) antigens. We used a 51Cr release assay to study the susceptibility of oligodendrocyte-enriched glial cells to MHC-restricted and non-restricted immune-mediated cytolysis. Mitogen-activated mononuclear cells induced significant lysis in a lectin-dependent cytotoxicity assay. Mononuclear cells allo-activated in a one-way mixed lymphocyte culture with E- cells from the glial cell donor induced a significantly higher degree of oligodendrocyte cytolysis than mononuclear cells activated with E- cells bearing MHC-class I antigens discordant with the glia. Cytolysis by alloactivated unfractionated lymphocytes and by purified CD8+ lymphocytes was reduced by an anti-class I antibody (W6/32). Our findings suggest that human oligodendrocytes can be susceptible targets for MHC class I-restricted lysis.

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