Uhlig Holm H, Coombes Janine, Mottet Christian, Izcue Ana, Thompson Claire, Fanger Andrea, Tannapfel Andrea, Fontenot Jason D, Ramsdell Fred, Powrie Fiona
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
J Immunol. 2006 Nov 1;177(9):5852-60. doi: 10.4049/jimmunol.177.9.5852.
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 behavior 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.
在小鼠结肠炎的T细胞转移模型中,CD4+CD25+调节性T细胞可预防和缓解肠道炎症。我们以Foxp3作为调节性T细胞活性的标志物,对野生型小鼠体内Foxp3+CD4+CD25+细胞的分布以及实验性结肠炎治愈过程中的情况进行了全面分析。在这两种情况下,均发现Foxp3+CD4+CD25+细胞在结肠和次级淋巴器官中积聚。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,这表明在炎症条件下,小鼠和人类调节性细胞的行为具有相似性。小鼠结肠炎的治愈依赖于IL-10的存在,并且在结肠炎治愈期间以及稳态条件下,产生IL-10的CD4+CD25+T细胞在结肠中均有富集。我们的数据表明,虽然表达Foxp3的CD4+CD25+T细胞存在于淋巴器官和结肠中,但产生IL-10的CD4+CD25+T细胞亚群主要存在于肠道固有层,这表明效应部位的调节性T细胞反应存在区室化。