TUMOR-NECROSIS-FACTOR-ALPHA INDUCTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN EXPRESSION IS INHIBITED BY INTERFERON-GAMMA IN AMONOCYTIC CELL-LINE

Regulation of major histocompatibility complex (MHC) class II antigen expression by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. The an alysis of class II gene regulation benefits greatly from the existence of mutants with defects in regulatory factors. We report the establis hment of a subclone of the human monocytic cell line U937, termed C119 /9, with unusual cytokine regulation of MHC class II expression. In co ntrast to the parental U937 cell line, only tumor necrosis factor (TNF )-alpha, and not interferon (IFN)-gamma induces the expression of MHC class II antigens on C119/9 cells, and paradoxically, this induction w as inhibited almost completely by IFN-gamma. The HLA-DR induction is c ontrolled at the transcriptional level by the first 150 bp of the clas s II promoter which contains all the class II consensus elements. Both HLA-DR and -DQ mRNA are induced by TNF-alpha treatment, and both are diminished upon co-treatment with TNF-alpha and IFN-gamma. This antago nism between TNF-alpha and IFN-gamma seem to be restricted to MHC clas s II genes. This subline of U937 cells may be useful in further studie s of MHC class II regulation.