Schistosoma japonicum egg antigens stimulate CD4+ CD25+ T cells and modulate airway inflammation in a murine model of asthma
Schistosoma japonicum egg antigens stimulate CD4+ CD25+ T cells and modulate airway inflammation in a murine model of asthma
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DOI：
10.1111/j.1365-2567.2006.02472.x
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发表时间：
2007-01
期刊：
影响因子：
6.4
通讯作者：
Jiang-hua Yang;Jiaqing Zhao;Yanfeng Yang;Lei Zhang;Xue Yang;Xiang Zhu;Minjun Ji;Nanxiong Sun;C. Su
中科院分区：
文献类型：
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作者：
Jiang-hua Yang;Jiaqing Zhao;Yanfeng Yang;Lei Zhang;Xue Yang;Xiang Zhu;Minjun Ji;Nanxiong Sun;C. Su
许多流行病学和临床研究表明，过敏和蠕虫感染之间存在负相关，例如血吸虫病。因此，我们推测日本血吸虫虫卵抗原是一种天然抗原，可以诱导具有调节活性的CD4+CD25+T细胞的产生，从而调节呼吸道炎症和抑制哮喘的发生。用流式细胞仪检测卵白蛋白(OVA)、CD25+耗竭/OVA、血吸虫卵抗原、血吸虫卵抗原/OVA处理的小鼠和对照组小鼠外周血中CD25+T细胞的百分率。在体内和体外研究了这些小鼠的CD25+T细胞抑制T细胞增殖和细胞因子产生的能力。结果显示，与对照组相比，OVA治疗组小鼠的CD4+CD25+T细胞对黏膜T辅助细胞2反应的调控能力降低(P<；0.05)。血吸虫卵抗原治疗可增加CD25+T细胞的数量和抑制活性，从而产生IL-10，但不产生IL-4。在哮喘小鼠模型中，日本血吸虫卵抗原减少Th2细胞因子的表达，减轻抗原诱导的呼吸道炎症，抑制哮喘的发生。因此，我们提供了日本血吸虫虫卵抗原诱导CD4+CD25+T细胞的产生，从而导致结构性免疫抑制活性和抑制哮喘发生的证据。这些结果揭示了一种预防哮喘的新形式，并对蠕虫感染对过敏发展的保护作用提出了一种机制解释。
A number of epidemiological and clinical studies have suggested an inverse association between allergy and helminth infection, such as Schistosomiasis. Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4+ CD25+ T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development. The frequency of CD4+ CD25+ T cells was determined by flow cytometry for mice treated with ovalbumin (OVA), CD25+ depletion/OVA, schistosome egg antigens, schistosome egg antigens/OVA and for control mice. The ability of CD25+ T cells from these mice to suppress T‐cell proliferation and cytokine production was investigated both in vivo and in vitro. Results showed that the CD4+ CD25+ T cells of OVA‐treated mice exhibited impaired control of dysregulated mucosal T helper 2 responses compared to the controls (P < 0·05). Depletion of CD25+ cells accelerated OVA‐induced airway inflammation and increased the expression of interleukin (IL)‐5 and IL‐4. Treatment with schistosome egg antigens increased the number and suppressive activity of CD4+ CD25+ T cells, which made IL‐10, but little IL‐4. In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen‐induced airway inflammation, and inhibited asthma development. Thus, we provided evidence that S. japonicum egg antigens induced the production of CD4+ CD25+ T cells, resulting in constitutive immunosuppressive activity and inhibition of asthma development. These results reveal a novel form of protection against asthma and suggest a mechanistic explanation for the protective effect of helminth infection on the development of allergy.