Interleukin-18 induces interferon-gamma production through NF-kappaB and NFAT activation in murine T helper type 1 cells
Tsuji-Takayama, K.; Aizawa, Y.; Okamoto, I.; Kojima, H.; Koide, K.; Takeuchi, M.; Ikegami, H.; Ohta, T.; Kurimoto, M.
Cellular Immunology 196(1): 41-50
1999
ISSN/ISBN: 0008-8749
PMID: 10486154
DOI: 10.1006/cimm.1999.1542
Accession: 010867543
Interleukin-18 (IL-18) combined with anti-CD3 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-kappaB in Th1 cells, it was not sufficient for the production of IFN-gamma. To examine the importance of NF-kappaB activation in IFN-gamma production, we established Th1 cells which expressed a transdominant IkappaBalpha mutant. In these cells, activation of NF-kappaB and production of IFN-gamma by IL-18 were suppressed. On the other hand, we examined the T cell receptor (TCR)/CD3-mediated signaling pathway. FK506, an inhibitor of NFAT activation, inhibited IFN-gamma production by IL-18 without any effect on the NF-kappaB activation. We conclude that dual signaling consisting of IL-18-induced NF-kappaB activation and TCR/CD3-mediated NFAT activation is crucial for IFN-gamma production by IL-18 in murine Th1 cells.