Previous results by ourselves and others demonstrated that brain cells and cell lines express major histocompatibility complex class II antigens. We examined interferon-gamma (IFN-γ)-mediated induction of human class II antigen expression on the glioma cells. Purified IFN-γ induced the expression of HLA-DR antigens on the surface of the glioma cell lines U-373 MG and U-105 MG. Concomitant increase of HLA-DR(α) and HLA-DC(β)-specific RNA in the cytoplasm was also observed after treatment with IFN-γ. Increases of class II antigen paralleled the increased level of class II-specific RNA. The effect of IFN-γ on the induction of human class II antigen expression was dose and time dependent. A marked induction of human class II antigen expression was observed when glioma cells were cultured with more than 100 U/ml of IFN-γ. Little or no induction was observed with less than 50 U/ml of IFN-γ. Compared to human blood monocytes, glioma cells needed higher concentrations of IFN-γ for the induction of class II antigen expression. In allogenic mixed lymphocyte cultures, the glioma cell line U-373 MG stimulated a mixed lymphocyte response (MLR). MLR-stimulating capacity was augmented by IFN-γ. THe concomitant augmentation of class II antigen levels and MLR-stimulating capacity suggests that the most relevant factor for MLR stimulation may be antigen density. This is the first report of MLR stimulation by a glioma cell line.
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