Antagonistic effect of interferon-beta on the interferon-gamma-induced expression of Ia antigen in murine macrophages

• Published in: The Journal of immunology (1950) Vol. 135; no. 3; pp. 1857 - 1863
• Main Authors: Ling, PD, Warren, MK, Vogel, SN
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.09.1985; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Cell interactions; DNA, Recombinant; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility Antigens Class II - immunology; Immunobiology; Indomethacin - pharmacology; Interferon Type I - pharmacology; Interferon-gamma - antagonists & inhibitors; Macrophages - immunology; Mice; Mice, Inbred C3H; Time Factors; Induction; Major histocompatibility system; Rodentia; Lymphokine; Ia-System; Biological activity; Vertebrata; Mammalia; Alloantigen; Mouse; Beta interferon; Antagonist; Gamma interferon; Macrophage
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.135.3.1857

The cell surface expression of I region-associated (Ia) antigens by murine and human macrophages has been shown by investigators from a number of laboratories to be induced in a dose-dependent fashion by IFN-gamma, which is free of other lymphokines. The experiments described in this report demonstrate that fibroblast-derived IFN-beta exerts an antagonistic effect on IFN-gamma induced Ia expression in murine macrophages. Simultaneous addition of IFN-beta and IFN-gamma to peritoneal exudate macrophages results in decreased Ia expression when compared with macrophages treated with IFN-gamma only. Different sources of highly purified IFN-beta, as well as a recombinant human IFN-alpha (A/D Bgl; shown previously to be as active as IFN-beta in several other murine systems) acted in a similar antagonistic fashion to IFN-gamma-induced Ia induction. The down-regulation of Ia expression by IFN-beta is dose-dependent over a concentration range up to 100 U/ml. Time-course experiments indicated that for IFN-beta to down-regulate IFN-gamma-induced Ia, it had to be present either before stimulation with IFN-gamma or during the first 24 hr of simultaneous stimulation. Further experiments in which a highly specific antibody against IFN-alpha/beta was added to the cultures confirmed the findings of the time-course experiments. Inhibitors of the arachidonic acid pathway failed to reverse the effect of IFN-beta to reduce Ia antigen expression, which suggests that this inhibition is not prostaglandin mediated. Thus, these findings support a role for type I IFN as naturally occurring substances that negatively regulate the expression of class II molecules.