Expression of the integrin αEβ7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells

Expression of the integrin αEβ7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells
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DOI:
10.1073/pnas.192162899
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发表时间:
2002-10-01
影响因子:
11.1
通讯作者:
Hamann, A
Hamann, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lehmann, J;Huehn, J;Hamann, A

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调节性CD25(+)CD4(+) T细胞被认为是T细胞稳态和自我耐受的重要参与者。在此,我们报道整合素ε(E)beta(7)可识别上皮钙粘蛋白,识别出最有效的调节性CD25(+) T细胞亚群。引人注目的是,CD25阴性α(E)(+)CD4(+) T细胞显示出调节活性。 α(E)(+) 亚群 CD25(+) 和 CD25(-) 均表达 CTLA-4,在体外抑制 T 细胞增殖,并在体内严重联合免疫缺陷模型 (SCID) 中保护小鼠免受结肠炎。 α(E)(+)CD25(+) T 细胞几乎不产生细胞因子,而 α(E)(+)CD25(-) T 细胞代表了一个独特的亚群,其中高 IL-2、IFN-γ 和 T 辅助细胞 2-细胞因子的产生与抑制功能相关。因此,整合素α(E)β(7)可以被视为高效、功能独特的调节性T细胞亚群的新标记物,这些调节性T细胞专门与上皮环境进行串扰。
Regulatory CD25(+)CD4(+) T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin epsilon(E)beta(7), which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25(+) T cells. Strikingly, CD25-negative alpha(E)(+)CD4(+) T cells displayed regulatory activity. Both alpha(E)(+) subsets, CD25(+) and CD25(-), express CTLA-4, suppress T cell proliferation in vitro, and protect mice from colitis in the severe combined immunodeficient model (SCID) in vivo. Whereas alpha(E)(+)CD25(+) T cells produce almost no cytokines, alpha(E)(+)CD25(-) T cells represent a unique subset in which high IL-2, IFN-gamma and T helper 2-cytokine production is linked with suppressive function. Thus, the integrin alpha(E)beta(7) can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.