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* Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom;
Children’s Hospital and
Institute of Pathology, University of Leipzig, Leipzig, Germany;
Department of Immunology, University of Washington, Seattle, WA 98195; and
¶ Zymogenetics, Seattle, WA 98102
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Wellcome Trust (to F.P. and C.T.), the Medical Research Council (to J.C.), Deutsche Forschungsgemeinschaft Grant HU 128-2 (to H.H.U.), the University of Leipzig (to H.H.U., F1-49), the Swiss National Fund (to C.M.), training grants from the National Institutes of Health and the Cancer Research Institute, and the Spanish Ministerio de Educacion y Ciencia (to A.I.).
2 H.H.U. and J.C. contributed equally.
3 Address correspondence and reprint requests to Dr. Fiona Powrie, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K. E-mail address: fiona.powrie{at}pathology.ox.ac.uk
4 Abbreviations used in this paper: TR, regulatory T cell; IBD, inflammatory bowel disease; MLN, mesenteric lymph node; LP, lamina propria; CD, Crohn’s disease; UC, ulcerative colitis; POD, peroxidase; MHC-II, MHC class II; DAPI, 4',6'-diamidino-2-phenylindole.
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