Anti-proliferative effect of IFN-gamma in immune regulation. II. IFN- gamma inhibits the proliferation of murine bone marrow cells stimulated with IL-3, IL-4, or granulocyte-macrophage colony-stimulating factor

• Published in: The Journal of immunology (1950) Vol. 141; no. 8; pp. 2635 - 2642
• Main Authors: Gajewski, TF, Goldwasser, E, Fitch, FW
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.10.1988; American Association of Immunologists
• Subjects: Adjuvants, Immunologic - pharmacology; Analysis of the immune response. Humoral and cellular immunity; Animals; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow Cells; Cell-Free System; Clone Cells - immunology; Clone Cells - metabolism; Colony-Stimulating Factors - biosynthesis; Colony-Stimulating Factors - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Inhibitors - pharmacology; Growth Substances - biosynthesis; Growth Substances - pharmacology; Hematopoiesis - drug effects; Immunobiology; Interferon-gamma - pharmacology; Interleukin-3 - biosynthesis; Interleukin-3 - pharmacology; Interleukin-4; Interleukins - biosynthesis; Interleukins - pharmacology; Lymphocyte Activation; Lymphokines - physiology; Lymphokines, interleukins ( function, expression); Mice; Mice, Inbred CBA; Recombinant Proteins - pharmacology; Regulatory factors and their cellular receptors; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Cell proliferation; Interleukin 4; Cell line; Interleukin 3; Bone marrow; Activation; Immune regulation; Lymphokine; Inhibition; Granulocyte macrophage colony stimulating factor; Gamma interferon
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.141.8.2635

A biphasic dose response curve was observed when the bone marrow-derived cell line FDCP1, used as an indicator line for IL-3 bioassays, was exposed to supernatants from some activated T cell clones but not others. The active component which inhibited proliferation at the higher supernatant concentrations appeared to be IFN-gamma, based on the following observations. 1) Only those culture supernatants which contained IFN-gamma gave a biphasic dose response curve; 2) with these supernatants, an anti-IFN-gamma mAb augmented the proliferation of FDCP1 cells at the higher supernatant concentrations; and 3) rIFN-gamma profoundly inhibited the proliferation of FDCP1 cells stimulated with rIL-3 or rIL-4. rTNF-alpha inhibited FDCP1 proliferation only to a modest extent, yet the combination of rTNF-alpha + rIFN-gamma provided greater inhibition than each agent alone. The proliferation of a second bone marrow-derived cell line, DA1, was not inhibited by rIFN-gamma or rIFN-gamma + rTNF-alpha when stimulated with rIL-3 or recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). Fresh bone marrow cells also showed a suboptimal proliferative response when stimulated with T cell supernatants containing IFN-gamma, and this response was augmented considerably upon the addition of anti-IFN-gamma mAb. Bone marrow cell proliferation was observed upon exposure to rIL-3, rIL-4, or rGM-CSF, and these responses were inhibited by rIFN-gamma; rTNF-alpha also produced a synergistic effect with these cells. Bone marrow cell colony formation stimulated by rIL-3 or rGM-CSF also was inhibited by rIFN-gamma. Colony formation in bone marrow cell cultures was not observed in response to rIL-4. Collectively, these results suggest that Th1 cells, which in addition to IL-3 and GM-CSF also produce IFN-gamma, may regulate hemopoietic cell proliferation and colony formation differently from the way Th2 cells do, which do not produce IFN-gamma.