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Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis

Yu, Qi T. BS; Saruta, Masayuki MD, PhD; Avanesyan, Armine BS1; Fleshner, Phillip R. MD2; Banham, Alison H. MA, D.Phil3; Papadakis, Konstantinos A. MD, PhD1*

doi: 10.1002/ibd.20053
Original Basic Science Articles: FOXP3+ Regulatory T Cells in UC: Original Article

Background CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental murine colitis but little is known about their potential role in human inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a critical role in the development and function of CD4+CD25+ TR. The aim of this study was to examine the presence and functional characteristics of TR cells in colonic lymphoid tissues in patients with ulcerative colitis (UC).

Methods FOXP3 expression was assessed by flow cytometry, immunohistochemistry, and reverse-transcriptase polymerase chain reaction (RT-PCR). Functional characterization of CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of cytokines by cocultured effector CD4+CD25 T cells.

Results FOXP3+CD4+ T cells are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous MLN CD4+CD25 T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells potently suppress the production of both Th1 (IFN-γ, IL-2) and Th2 (IL-5, IL-13) cytokines by cocultured CD4+CD25 T cells. FOXP3+ cells localized in the T-cell-rich areas of MLN and occasionally present in the follicles.

Conclusions There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC. CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in spite of active mucosal inflammation. These data suggest that their suppressor activity may be abrogated in vivo or they are unable to counterbalance the chronic mucosal inflammation in UC.

(Inflamm Bowel Dis 2007)

1Burns and Allen Research Institute, Division of Gastroenterology and Inflammatory Bowel Disease Center, Los Angeles, CA, USA

2Division of Colorectal Surgery, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA

3Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, UK

*Cedars-Sinai Medical Center, 8700 Beverly Blvd., D-4063, Los Angeles CA 90048


Received for publication 19 July 2006; Accepted 26 October 2006

Published online 21 December 2006 in Wiley InterScience (

Grant sponsor: Broad Medical Research Program in Inflammatory Bowel Diseases by the Eli and Edythe L. Broad Foundation; Grant sponsor: Leukaemia Research Fund.

Preliminary results were presented at the American Association of Immunologist annual meeting, 12–16 May 2006, Boston, MA, and the abstract has been published in the Journal of Immunology 2006;S224:110.1, at Digestive Disease Week, 20–25 May 2006, Los Angeles, CA, and the abstract has been published in Gastroenterology 130 (2006) #599:P-108 and the Federation of Clinical Immunology Societies (FOCIS) meeting, 1–5 June 2006, San Francisco, CA.

§The first two authors contributed equally to this work and should be considered joint first authors.

© Crohn's & Colitis Foundation of America, Inc.
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