Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells

Koji Uraushihara, Takanori Kanai, Kwibeom Ko, Teruji Totsuka, Shin Makita, Ryoichi Iiyama, Tetsuya Nakamura, Mamoru Watanabe

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

CD4+CD25+ regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance and prevention of autoimmune disease. However, accumulating evidence suggests that a fraction of the peripheral CD4+CD25- T cell population also possesses regulatory activity in vivo. Recently, it has been shown glucocorticoid-induced TNFR family-related gene (GITR) is predominantly expressed on CD4+CD25+ regulatory T cells. In this study, we show evidence that CD4+GITR+ T cells, regardless of the CD25 expression, regulate the mucosal immune responses and intestinal inflammation. SCID mice restored with the CD4+GITR- T cell population developed wasting disease and severe chronic colitis. Cotransfer of CD4+GITR+ population prevented the development of CD4+CD45RBhigh T cell-transferred colitis. Administration of anti-GITR mAb-induced chronic colitis in mice restored both CD45RBhigh and CD45RBlow CD4+ T cells. Interestingly, both CD4+CD25+ and CD4+CD25- GITR+ T cells prevented wasting disease and colitis. Furthermore, in vitro studies revealed that CD4+CD25-GITR+ T cells as well as CD4+CD25+GITR+ T cells expressed CTLA-4 intracellularly, showed anergic, suppressed T cell proliferation, and produced IL-10 and TGF-β. These data suggest that GITR can be used as a specific marker for regulatory T cells controlling mucosal inflammation and also as a target for treatment of inflammatory bowel disease.

Original languageEnglish
Pages (from-to)708-716
Number of pages9
JournalJournal of Immunology
Volume171
Issue number2
Publication statusPublished - 2003 Jul 15
Externally publishedYes

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Tumor Necrosis Factor Receptors
Regulatory T-Lymphocytes
Inflammatory Bowel Diseases
Glucocorticoids
T-Lymphocytes
Colitis
Genes
Chronic Wasting Disease
Population
Wasting Syndrome
Inflammation
Self Tolerance
Mucosal Immunity
SCID Mice
Interleukin-10
Autoimmune Diseases
Cell Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells. / Uraushihara, Koji; Kanai, Takanori; Ko, Kwibeom; Totsuka, Teruji; Makita, Shin; Iiyama, Ryoichi; Nakamura, Tetsuya; Watanabe, Mamoru.

In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 708-716.

Research output: Contribution to journalArticle

Uraushihara, K, Kanai, T, Ko, K, Totsuka, T, Makita, S, Iiyama, R, Nakamura, T & Watanabe, M 2003, 'Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells', Journal of Immunology, vol. 171, no. 2, pp. 708-716.
Uraushihara, Koji ; Kanai, Takanori ; Ko, Kwibeom ; Totsuka, Teruji ; Makita, Shin ; Iiyama, Ryoichi ; Nakamura, Tetsuya ; Watanabe, Mamoru. / Regulation of murine inflammatory bowel disease by CD25+ and CD25- CD4+ glucocorticoid-induced TNF receptor family-related gene+ regulatory T cells. In: Journal of Immunology. 2003 ; Vol. 171, No. 2. pp. 708-716.
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