INTERFERON-GAMMA-INDUCING FACTOR, A NOVEL CYTOKINE, ENHANCES FAS LIGAND-MEDIATED CYTOTOXICITY OF MURINE T-HELPER-1 CELLS

Fas ligand (FasL), expressed on activated T cells, plays a central rol e in regulating the immune response by inducing apoptosis in activated lymphocytes through binding to its receptor, Fas. We report here that a newly discovered cytokine, interferon-gamma-inducing factor (IGIF) (H. Okamura et al., Nature 378, 88, 1995), selectively enhances the Fa sL-mediated cytotoxicity of cloned murine Th1 cells, but not Th0 or Th 2 cells. Anti-IFN-gamma antibody (Ab) did mot block the IGIF-induced c ytotoxicity of Th1 cells, nor did IFN-alpha, IFN-gamma, or TNF-alpha a ugment the cytotoxic activity of Th1, thus indicating that this enhanc ed cytotoxicity of Th1 cells was mediated by IGIF. In addition, IL-12 was also found to enhance the Fast-mediated cytotoxicity of Th1 cells, suggesting that Th1 cells possesses receptors for both cytokines alth ough these cytokines can act via different pathways. The results thus show that IGIF, recently proposed as IL-18, might play a potential rol e in immunoregulation or in inflammation by augmenting the functional activity of FasL on Th1 cells. (C) 1996 Academic Press, Inc.