Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis.

Characterization of Foxp3+CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis.
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DOI:
10.4049/jimmunol.177.9.5852
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发表时间:
2006-11-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Powrie F
Powrie F
中科院分区:
其他
文献类型:
--
作者:
Uhlig HH;Coombes J;Mottet C;Izcue A;Thompson C;Fanger A;Tannapfel A;Fontenot JD;Ramsdell F;Powrie F

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在小鼠结肠炎T细胞转移模型中,CD4+CD25+调节性T细胞可以预防和缓解肠道炎症。利用Foxp3作为调节性T细胞活性的标志物,我们现在全面分析了Foxp3+CD4+CD25+细胞在野生型小鼠体内的分布以及实验性结肠炎的治愈过程。在这两个病例中,Foxp3+CD4+CD25+细胞均聚集在结肠和次级淋巴器官中。重要的是,在溃疡性结肠炎或克罗恩病患者的结肠样本中,Foxp3+细胞的密度增加,这表明小鼠和人类调节细胞在炎症条件下的行为相似。小鼠结肠炎的治愈依赖于IL-10的存在,在结肠炎治愈过程中和在稳态条件下,产生IL-10的CD4+CD25+T细胞在结肠内都得到了丰富。我们的数据表明,尽管表达Foxp3的CD4+CD25+T细胞存在于淋巴器官和结肠内,但产生IL-10的CD4+CD25+T细胞的亚群主要存在于肠道固有层,这表明调节性T细胞在效应部位的反应是分开的。
CD4+CD25+ regulatory T cells can prevent and resolve intestinal inflammation in the murine T cell transfer model of colitis. Using Foxp3 as a marker of regulatory T cell activity, we now provide a comprehensive analysis of the in vivo distribution of Foxp3+CD4+CD25+ cells in wild-type mice, and during cure of experimental colitis. In both cases, Foxp3+CD4+CD25+ cells were found to accumulate in the colon and secondary lymphoid organs. Importantly, Foxp3+ cells were present at increased density in colon samples from patients with ulcerative colitis or Crohn’s disease, suggesting similarities in the behaviour of murine and human regulatory cells under inflammatory conditions. Cure of murine colitis was dependent on the presence of IL- 10, and IL-10-producing CD4+CD25+ T cells were enriched within the colon during cure of colitis and also under steady state conditions. Our data indicate that although CD4+CD25+ T cells expressing Foxp3 are present within both lymphoid organs and the colon, subsets of IL- 10-producing CD4+CD25+ T cells are present mainly within the intestinal lamina propria suggesting compartmentalization of the regulatory T cell response at effector sites.
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