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

被引:370
作者
Uhlig, Holm H.
Coombes, Janine
Mottet, Christian
Izcue, Ana
Thompson, Claire
Fanger, Andrea
Tannapfel, Andrea
Fontenot, Jason D.
Ramsdell, Fred
Powrie, Fiona
机构
[1] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[2] Univ Leipzig, Childrens Hosp, D-7010 Leipzig, Germany
[3] Univ Leipzig, Inst Pathol, D-7010 Leipzig, Germany
[4] Univ Washington, Dept Immunol, Seattle, WA 98195 USA
[5] Zymogenetics, Seattle, WA 98102 USA
基金
英国惠康基金;
关键词
D O I
10.4049/jimmunol.177.9.5852
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-10producing 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.
引用
收藏
页码:5852 / 5860
页数:9
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