Immune responses to Nippostrongylus brasiliensis and tuberculin protein in GATA-3-transgenic mice
Immune responses to Nippostrongylus brasiliensis and tuberculin protein in GATA-3-transgenic mice
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DOI：
10.1016/j.imlet.2005.03.005
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Watanabe, N
中科院分区：
文献类型：
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作者：
Ozawa, H;Tamauchi, H;Watanabe, N
GATA-3似乎是Th2反应的关键。然而，很少有体内实验研究GATA-3在Th1和Th2免疫应答中的功能。我们培育了两种含有SR α或lck启动子的gata -3转基因（Tg）小鼠，并检测了感染巴西尼波线虫小鼠的Th2免疫应答和纯化结核素（PPD）免疫的Th1免疫应答。所有GATA-3-Tg小鼠外周血嗜酸性粒细胞在首次感染后增加10- 20倍，在继发感染后增加25-100倍。感染GATA-3-Tg小鼠的嗜酸性粒细胞数量显著高于感染对照组。GATA-3-Tg小鼠初次感染后总i - e水平升高8-450倍，明显高于对照组。感染GATA-3-Tg小鼠的肠系膜淋巴结细胞在巴西隐孢子虫抗原刺激下分泌的IL-5和IL-13高于对照组。然而，在GATA-3-Tg和对照组之间，IL-4和ifn - γ的产生是相当的。经PPD免疫的小鼠皮下注射PPD诱导延迟型超敏反应（DTH）。GATA-3-Tg小鼠DTH反应引起的足垫肿胀量明显小于对照组。体外PPD刺激GATA-3-Tg小鼠腹股沟淋巴结细胞分泌IL-5、IL-10和ifn - γ的水平均高于对照组。这些结果表明，Th1和Th2驱动的条件通过直接结合GATA-3到IL-5启动子区域来促进GATA-3- tg小鼠IL-5的产生。GATA-3对IL-13、ifn - γ和IL-10产生的影响因刺激条件的不同而不同。然而，在GATA-3-Tg小鼠中，IL-4的产生并没有显著升高，这表明IL-4和IL-5的产生在这些小鼠中受到差异调节。(c) 2005 Elsevier B.V.版权所有
GATA-3 appears to be key to the Th2 response. However, few in vivo experiments have examined the function of GATA-3 in Th1 and Th2 immune responses. We developed two lines of GATA-3-transgenic (Tg) mice harboring the SR alpha or lck promoters and examined the Th2 immune responses of mice infected with the intestinal nematode Nippostrongylus brasiliensis and the Th1 responses with purified derivative of tuberculin (PPD) immunization. Numbers of peripheral blood eosinophils in all GATA-3-Tg mice increased 10- to 20-fold after primary infection with N. brasiliensis and 25-100-fold after secondary infection. The number of eosinophils in infected GATA-3-Tg mice was significantly higher than that in infected control littermates. Total I.-E levels after primary infection in GATA-3-Tg mice were 8-450-fold increased, which was significantly higher than those of control mice. Mesenteric lymph node cells of infected GATA-3-Tg mice upon stimulation with N. brasiliensis antigen secreted more IL-5 and IL-13 than those of control mice. However, production of IL-4 and IFN-gamma were comparable between GATA-3-Tg and controls.Mice immunized with PPD were intradermally challenged with PPD to induce delayed type hypersensitivity (DTH). The amount of footpad swelling caused by the DTH reaction in GATA-3-Tg mice was significantly smaller than that of control littermates. Inguinal lymph node cells from GATA-3-Tg mice stimulated with PPD in vitro secreted more IL-5, IL-10 and less IFN-gamma than those of control littermates.These results suggested that Th1 and Th2 driven conditions enhance IL-5 production in GATA-3-Tg mice through the direct binding of GATA-3 to the IL-5 promoter region. The influence of GATA-3 on IL-13, IFN-gamma and IL-10 production varied according to the stimulating conditions. However, IL-4 production was not significantly elevated in GATA-3-Tg mice, indicating that IL-4 and IL-5 production was differentially regulated in these mice. (c) 2005 Elsevier B.V. All rights reserved.