Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells.
Gamma-Interferon (IFN-gamma) is a lymphokine produced by T lymphocytes. We find that recombinant human IFN-gamma induces expression of HLA-D antigens on human promyelocytic leukemia cells (HL-60) and enhances expression of HLA-D antigens on normal human monocytes and macrophages. Induction of both HLA-D antigen expression and HLA-D mRNA accumulation occurs within 1 day of exposure of HL-60 to IFN-gamma and is maximal by day 5. Maximal antigen expression occurs in the presence of 100-500 units of IFN-gamma per ml. IFN-gamma induces expression of DR but not DC antigens on HL-60, as confirmed by using four different murine monoclonal antibodies or one rabbit heterologous antibody. RNA blot data show that IFN-gamma-exposed HL-60 cells contain mRNA for DR alpha and DR beta polypeptides but not for DC alpha and DC beta polypeptides, which also suggests that HLA-DR and HLA-DC gene regions can be independently regulated. IFN-gamma induces 20% of HL-60 cells to differentiate to macrophage-like cells. However, IFN-gamma dose-response studies using both HL-60 cells and a nondifferentiation variant of HL-60 cells (HL-60 blast) clearly show that induction of transcription and expression of HLA-D gene products by IFN-gamma can be uncoupled from expression of other monocyte-macrophage characteristics. Further studies show that IFN-gamma enhances expression of HLA-D antigens on normal human monocytes and macrophages. Expression of the HLA-D antigens is necessary for the interaction of macrophages and T lymphocytes; IFN-gamma may play a fundamental role in this interaction.
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017977:Deltaretrovirus / Q000276:immunology; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D012333:RNA, Messenger; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate