Cutting edge: IL-18-transgenic mice: In vivo evidence of a broad role for IL-18 in modulating immune function

Cutting edge: IL-18-transgenic mice: In vivo evidence of a broad role for IL-18 in modulating immune function
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DOI:
10.4049/jimmunol.166.12.7014
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发表时间:
2001-06-15
影响因子:
4.4
通讯作者:
Oizumi, K
Oizumi, K
中科院分区:
医学2区
文献类型:
--
作者:
Hoshino, T;Kawase, Y;Oizumi, K

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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细胞和NK细胞中存在Th 2细胞因子IL-13的协同诱导。最近,我们和其他研究小组报告说,IL-18可以潜在地诱导IgE,IgG 1,和Th 2细胞因子在小鼠实验模型的生产。在这里,我们报告的一代IL-18转基因(Tg)小鼠中,成熟的小鼠IL-18 cDNA表达。在这些小鼠中,CD 8(+)CD 44(高)T细胞和巨噬细胞增加,但B细胞减少,而血清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 cofactor 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. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA 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-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wildtype mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.