Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice
Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice
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DOI：
10.1128/iai.01269-12
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发表时间：
2013-03-01
影响因子：
3.1
通讯作者：
Eaton, Kathryn A.
中科院分区：
文献类型：
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作者：
Gray, Brian M.;Fontaine, Clinton A.;Eaton, Kathryn A.
由胃病原体幽门螺杆菌引起的疾病的严重程度从无症状到消化性溃疡和癌症不等。越来越多的证据表明，这种变异的一个来源是异常的宿主反应。本研究的目的是使用H. pylori胃炎，以研究调节性T细胞（Treg）以及促炎性T细胞（Th 1和Th 17）在胃炎、胃T细胞植入和胃细胞因子产生中的作用。我们的研究结果支持发表的数据表明，严重的胃炎在T细胞受体小鼠是由于Treg植入失败，Treg改善胃炎，和促炎反应是由于几个细胞亚群和细胞因子之间的相互作用。我们证实γ干扰素（IFN-γ）是诱导胃炎所必需的，但表明IFN-γ产生的CD 4 T细胞是不必要的。白细胞介素17 A（IL-17 A）也有助于胃炎，但程度低于IFN-γ。肿瘤坏死因子α（TNF-α）和IL-17 F也与疾病相关升高。这些结果表明，H.幽门螺杆菌特异性CD 4（+）T细胞和IFN-γ在H.在幽门螺杆菌中，T细胞产生IFN-γ不是必需的。其他促炎细胞因子，如IL-17 F和TNF-α，在该模型中显示升高，也可能有助于诱导疾病。我们认为H.幽门螺杆菌与免疫调节的丧失和几种细胞因子和细胞亚群的改变有关，不能归因于单一的免疫途径。
Disease due to the gastric pathogen Helicobacter pylori varies in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model of H. pylori gastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-gamma) is essential for induction of gastritis but showed that IFN-gamma-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-gamma. Tumor necrosis factor alpha (TNF-alpha) and IL-17F were also elevated in association with disease. These results indicate that while H. pylori-specific CD4(+) T cells and IFN-gamma are both essential for induction of gastritis due to H. pylori, IFN-gamma production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-alpha, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due to H. pylori is associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.