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

Qi T. Yu, Masayuki Saruta, Armine Avanesyan, Phillip R. Fleshner, Alison H. Banham, Konstantinos Papadakis

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Background: CD4+CD25+ regulatory T cells (T R) 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 T R 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+CD259+ T cells potently suppress the production of both Thl (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.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalInflammatory Bowel Diseases
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2007
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Ulcerative Colitis
T-Lymphocytes
Lymph Nodes
Lymphoid Tissue
Cytokines
Colon
Mucous Membrane
Inflammation
Interleukin-13
Interleukin-5
Colitis
Reverse Transcriptase Polymerase Chain Reaction
Inflammatory Bowel Diseases
Interleukin-2
Flow Cytometry
Transcription Factors
Immunohistochemistry
Messenger RNA

Keywords

  • Colitis
  • Cytokines
  • FOXP3 protein
  • Regulatory
  • T-lymphocytes
  • Ulcerative

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Expression and functional characterization of FOXP3+CD4 + regulatory T cells in ulcerative colitis. / Yu, Qi T.; Saruta, Masayuki; Avanesyan, Armine; Fleshner, Phillip R.; Banham, Alison H.; Papadakis, Konstantinos.

In: Inflammatory Bowel Diseases, Vol. 13, No. 2, 01.02.2007, p. 191-199.

Research output: Contribution to journalArticle

Yu, Qi T. ; Saruta, Masayuki ; Avanesyan, Armine ; Fleshner, Phillip R. ; Banham, Alison H. ; Papadakis, Konstantinos. / Expression and functional characterization of FOXP3+CD4 + regulatory T cells in ulcerative colitis. In: Inflammatory Bowel Diseases. 2007 ; Vol. 13, No. 2. pp. 191-199.
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abstract = "Background: CD4+CD25+ regulatory T cells (T R) 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 T R 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+CD259+ T cells potently suppress the production of both Thl (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.",
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T1 - Expression and functional characterization of FOXP3+CD4 + regulatory T cells in ulcerative colitis

AU - Yu, Qi T.

AU - Saruta, Masayuki

AU - Avanesyan, Armine

AU - Fleshner, Phillip R.

AU - Banham, Alison H.

AU - Papadakis, Konstantinos

PY - 2007/2/1

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N2 - Background: CD4+CD25+ regulatory T cells (T R) 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 T R 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+CD259+ T cells potently suppress the production of both Thl (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.

AB - Background: CD4+CD25+ regulatory T cells (T R) 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 T R 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+CD259+ T cells potently suppress the production of both Thl (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.

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KW - T-lymphocytes

KW - Ulcerative

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