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.
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.
Gajewski
T F
TF
Department of Pathology, University of Chicago, IL 60637.
Goldwasser
E
E
Fitch
F W
FW
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002474:Cell-Free System; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006131:Growth Inhibitors / Q000494:pharmacology*; D006133:Growth Substances / Q000096:biosynthesis / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D007377:Interleukin-3; D007378:Interleukins; D008222:Lymphokines; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor