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 acti vation 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, w hile IGIF increased the IFN-gamma production by antigen-stimulated T c ell 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 stimu lated with Ag on B cell APC, immobilized anti-CD3, Con A, or IL-2 to a ugment IFN-gamma production and to induce IL-2R alpha-chain expression and proliferation of the Th1 clones, whereas IGIF had little or no ef fect on the IL-4 production and proliferation of Th2 clones stimulated with anti-CD3 or Ag. However, IGIF synergized with IL-12 to further a ugment the IFN-gamma production of the Th1 clones. Even in the presenc e of saturated amounts of IL-12, IGIF still augmented the IFN-gamma pr oduction and proliferation and enhanced the IL-2R alpha-chain expressi on of the Th1 clones. In contrast with IL-12, IGIF induced IL-2 produc tion by Ag- or anti-CD3-stimulated Th1 clones. These two findings indi cate that IGIF and IL-12 are utilizing different signal transduction p athways. We also found that IGIF as well as IL-12 was endogenously rel eased 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.