Tsuji-Takayama K, Aizawa Y, Okamoto I, Kojima H, Koide K, Takeuchi M, Ikegami H, Ohta T, Kurimoto M
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, Okayama, 702-8006, Japan.
Cell Immunol. 1999 Aug 25;196(1):41-50. doi: 10.1006/cimm.1999.1542.
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.
白细胞介素-18（IL-18）与抗CD3单克隆抗体（mAb）联合可诱导1型辅助性T细胞（Th1细胞）产生γ干扰素（IFN-γ）。单独使用IL-18或抗CD3 mAb均不能诱导IFN-γ的产生。尽管单独用IL-18处理可诱导Th1细胞中NF-κB的完全活化，但这对于IFN-γ的产生并不充分。为了研究NF-κB活化在IFN-γ产生中的重要性，我们构建了表达显性负性IκBα突变体的Th1细胞。在这些细胞中，IL-18介导的NF-κB活化和IFN-γ产生均受到抑制。另一方面，我们研究了T细胞受体（TCR）/CD3介导的信号通路。NFAT活化抑制剂FK506可抑制IL-18诱导的IFN-γ产生，但对NF-κB活化没有任何影响。我们得出结论，由IL-18诱导的NF-κB活化和TCR/CD3介导的NFAT活化组成的双重信号对于IL-18在小鼠Th1细胞中诱导IFN-γ产生至关重要。
