The first two authors contributed equally to this work and should be considered joint first authors.
Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis†
Version of Record online: 21 DEC 2006
Copyright © 2006 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 13, Issue 2, pages 191–199, February 2007
How to Cite
Yu, Q. T., Saruta, M., Avanesyan, A., Fleshner, P. R., Banham, A. H. and Papadakis, K. A. (2007), Expression and functional characterization of FOXP3+CD4+ regulatory T cells in ulcerative colitis. Inflamm Bowel Dis, 13: 191–199. doi: 10.1002/ibd.20053
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.
- Issue online: 12 JAN 2007
- Version of Record online: 21 DEC 2006
- Manuscript Accepted: 26 OCT 2006
- Manuscript Received: 19 JUL 2006
- Broad Medical Research Program in Inflammatory Bowel Diseases by the Eli and Edythe L. Broad Foundation
- Leukaemia Research Fund
- FOXP3 protein;
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)