Interleukin-18 induces interferon-γ production through NF-κB and NFAT activation in murine T helper type 1 cells

Interleukin-18 (IL-18) combined with anti-CDS monoclonal antibody (mAb) induced interferon-gamma (IFN-gamma) production by T helper type 1 (Th1) cells. Neither IL-18 nor anti-CD3 mAb alone induced production of IFN-gamma. Although treatment with IL-18 alone induced full activation of NF-kappa B in Th1 cells, it was not sufficient for the production of IFN-gamma, To examine the importance of NF-kappa B activation in IFN-gamma production, we established Th1 cells which expressed a transdominant I kappa B alpha mutant. In these cells, activation of NF-kappa B and production of IFN-gamma by IL-18 were suppressed. On the other hand, we examined the T cell receptor (TCR)I CD3-mediated signaling pathway. FK506, an inhibitor of NFAT activation, inhibited IFN-gamma production by IL-18 without any effect on the NF-KB activation. We conclude that dual signaling consisting of IL-18-induced NF-kappa B activation and TCR/CD3-mediated NFAT activation is crucial for IFN-gamma production by IL-18 in murine Th1 cells. (C) 1999 Academic Press.