Transforming growth factor β induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis
Transforming growth factor β induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis
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DOI：
10.1136/gut.2005.072801
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发表时间：
2006-05-01
期刊：
影响因子：
24.5
通讯作者：
Neurath, MF
中科院分区：
文献类型：
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作者：
Fantini, MC;Becker, C;Neurath, MF
背景与目的：效应性T细胞与调节性T细胞之间的失衡在炎症性肠病的发病机制中起着核心作用。除了胸腺外，外周血中的CD25-T细胞群可以通过转化生长因子-β诱导出CD4+CD25+调节性T细胞。在此，我们分析了转化生长因子-β诱导的调节性T细胞(Ti-Treg)在实验性结肠炎中的体内功能。方法：在有或没有转化生长因子-β的情况下，在细胞培养中产生Ti-Treg细胞，并利用CD4+CD62L+T细胞转移模型检测其在实验性结肠炎中的调节作用。结果：高分辨内窥镜、组织学、免疫组织化学和细胞因子分析显示，在体内，Ti-Treg细胞显著抑制Th1介导的结肠炎对CD4+CD62L+T细胞的转移。对体内和体外扩增的Ti-Treg细胞的进一步分析表明，外源性IL-2对这些细胞的存活和扩增至关重要。结论：我们的数据表明，调节性的Ti-Treg细胞通过转化生长因子-β和炎症部位效应性T细胞来源的外源性IL-2来扩张。除了TR1和胸腺的CD4+CD25+T细胞外，外周血中的Ti-Treg细胞是一类在T细胞介导的慢性肠炎中具有治疗潜力的调节性T细胞。
Background and aims: The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+ CD25+ regulatory T cells can be induced in the periphery from a population of CD25-T cells by treatment with transforming growth factor b (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis.Methods: Ti-Treg cells were generated in cell culture in the presence or absence of TGF-beta and tested for their regulatory potential in experimental colitis using the CD4+ CD62L+ T cell transfer model.Results: Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+ CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells.Conclusion: Our data suggest that regulatory Ti-Treg cells expand by TGF-beta and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+ CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.