Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells.

Abstract

.gamma.-Interferon (IFN-.gamma.) is a lymphokine produced by T lymphocytes. 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 U of IFN-.gamma./ml. IFN-.gamma. induces expression of DR but not DC antigens on HL-60, as confirmed by using 4 different murine monoclonal antibodies or 1 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. 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. 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.