IFN-gamma-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12.
We have previously reported the cloning of a novel cytokine, IFN-gamma-inducing factor (IGIF), which shared some biologic activities with IL-12. In this study, we analyzed the effects of murine IGIF on the activation of T cells, and compared the effects with those of IL-12. IGIF alone had no effect on the activation of T cell lines or Th1 clones, while IGIF increased the IFN-gamma production by antigen-stimulated T cell lines, but had no effect on IL-4 or IL-10 production. As reported with IL-12, IGIF served as a costimulatory factor for Th1 clones stimulated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to augment IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation of the Th1 clones, whereas IGIF had little or no effect on the IL-4 production and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF synergized with IL-12 to further augment the IFN-gamma production of the Th1 clones. Even in the presence of saturated amounts of IL-12, IGIF still augmented the IFN-gamma production and proliferation and enhanced the IL-2R alpha-chain expression of the Th1 clones. In contrast with IL-12, IGIF induced IL-2 production by Ag- or anti-CD3-stimulated Th1 clones. These two findings indicate that IGIF and IL-12 are utilizing different signal transduction pathways. We also found that IGIF as well as IL-12 was endogenously released through interaction between Th1 cells and spleen cell APC in the presence of specific Ag, and that it regulated IFN-gamma production. These results further suggest that IGIF may act as an immunoregulatory factor in the immune response.
Kohno
K
K
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Kataoka
J
J
Ohtsuki
T
T
Suemoto
Y
Y
Okamoto
I
I
Usui
M
M
Ikeda
M
M
Kurimoto
M
M
D000818:Animals; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D005260:Female; D007369:Interferon Inducers / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D007369:Interferon Inducers; D020382:Interleukin-18; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin