Induction of colitis by a CD4+ T cell clone specific for a bacterial epitope
Induction of colitis by a CD4+ T cell clone specific for a bacterial epitope
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DOI：
10.1073/pnas.2534546100
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发表时间：
2003-12-23
影响因子：
11.1
通讯作者：
Sher, A
中科院分区：
文献类型：
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作者：
Kullberg, MC;Andersen, JF;Sher, A
肠道植物群在炎症性肠病（IBD）的发病机制中起着重要作用。然而，在这个过程中，细菌是否作为免疫反应的唯一目标，或者它们是否通过触发抗自身反应间接起作用，目前还不清楚。我们以前已经表明，特定的病原体无IL-10缺陷（IL-10 KO）小鼠发展T辅助细胞（Th 1）-细胞因子相关的结肠炎实验感染肝杆菌后。本文证明H. Hepaticus Ag（SHelAg）特异性CD 4（+）Th 1克隆将疾病转移到H.肝感染的T细胞缺陷型RAG KO宿主。重要的是，SHelAg特异性克隆的未感染受体不会发生肠道炎症，并且对照曼氏血吸虫特异性Th 1克隆在转移到感染的RAG KO小鼠后不会诱导结肠炎。诱导疾病的T细胞克隆识别某些螺杆菌特异性表达的抗原（Ag），因为它们在体外用H.但当与来自幽门螺杆菌、各种非幽门螺杆菌的Ag制剂或与来自未感染小鼠的盲肠细菌裂解物一起培养时，则不会。对其中一个克隆的Ag特异性的表征表明，它与H. I-A（B）型肝细胞。总之，我们的研究结果表明，结肠炎可以诱导的克隆T细胞群体，是高度特异性的目标抗原对肠道细菌，这表明针对肠道植物群的异常T细胞反应是足以触发IBD。
It is now well established that the intestinal flora plays an important role in the pathogenesis of inflammatory bowel disease (IBD). However, whether bacteria serve as the sole target of the immune response in this process or whether they act indirectly by triggering an anti-self response is still unclear. We have previously shown that specific pathogen-free IL-10-deficient (IL-10 KO) mice develop a T helper (Th1)-cytokine associated colitis after experimental infection with Hehcobacter hepaticus. We here show that H. hepaticus Ag (SHelAg)-specificCD4(+) Th1 clones transfer disease to H. hepaticus-infected T cell-deficient RAG KO hosts. Importantly, uninfected recipients of the SHelAg-specific clones did not develop intestinal inflammation, and a control Schistosoma mansonispecific Th1 clone did not induce colitis upon transfer to infected RAG KO mice. The disease-inducing T cell clones recognized antigen(s) (Ag) specifically expressed by certain Helicobacter species as they responded when stimulated in vitro with H. hepaticus and Helicobacter typhlonius Ag, but not when cultured with Ag preparations from Helicobacter pylori, various non-helicobacter bacteria, or with cecal bacterial lysate from uninfected mice. Characterization of the Ag specificity of one of the clones showed that it reacts uniquely with a 15-mer peptide epitope on the flagellar hook protein (FlgE) of H. hepaticus presented by I-A(b). Together, our results demonstrate that colitis can be induced by clonal T cell populations that are highly specific for target Ag on intestinal bacteria, suggesting that an aberrant T cell response directed against gut flora is sufficient to trigger IBD.