Molecular immunological analysis for IgE production and a unique NK cell population producing type 2 cytokine, IL-13

IL-18已被证明是Th 1 T细胞发育的强辅助因子。然而，我们先前证明，当IL-18与IL-2组合时，在T和NK细胞中存在Th 2细胞因子IL-13的协同诱导（T.Hoshino，J. Immunol.162：5070，1999）。最近，我们和其他小组已经报道IL-18可以在鼠实验模型中潜在地诱导IgE、IgG 1和Th 2细胞因子产生（T.Hoshino，Eur.免疫学杂志30：1998，2000）。在此，我们报道了IL-18转基因（Tg）小鼠的产生，其中表达了与小鼠IG κ链的信号肽融合的小鼠成熟IL-18 cDNA。CD 8 ^+ CD 44 ^<high>T细胞和巨噬细胞增加，B细胞减少，血清IgE、IgG 1、IL-4和IFN-γ水平显著升高。IL-18 Tg小鼠中的脾T细胞产生比对照野生型小鼠更高水平的IFN-γ、IL-4、IL-5和IL-13。因此，体内IL-18的异常表达导致Th 1和Th 2细胞因子的产生增加。

IL-18 has been shown to be a strong co-factor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells (T.Hoshino, J.Immunol. 162 : 5070, 1999). More recently, we and other groups have reported IL-18 can potentially induce IgE, IgG1 and Th2 cytokine production in murine experimental models (T.Hoshino, Eur. J.Immunol. 30 : 1998, 2000).Here we report on the generation of IL-18 transgenic (Tg) mice in which mouse mature IL-18 cDNA fused to the signal peptide of the mouse Ig κ-chain was expressed. CD8^+ CD44^<high> T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4 and IFN-γ levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-γ, IL-4, IL-5 and IL-13 than control wild type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.