CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells

Shin Makita, Takanori Kanai, Shigeru Oshima, Koji Uraushihara, Teruji Totsuka, Taisuke Sawada, Tetsuya Nakamura, Kazutaka Koganei, Tsuneo Fukushima, Mamoru Watanabe

Research output: Contribution to journalArticle

211 Citations (Scopus)

Abstract

It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4+CD25 bright T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4+ T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly. Although LP CD4+CD25- T cells showed an activated and anergic/memory phenotype, they did not retain regulatory activity. In LP CD4+CD25+ T cells, however, cells expressing CD25 at high levels (CD4+CD25bright) suppressed the proliferation and various cytokine productions of CD4+CD25- T cells. LP CD4+CD25bright T cells by themselves produced fewer amounts of IL-2, IFN-γ, and IL-10. Interestingly, LP CD4 +CD25bright T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4+CD25bright T cells found in the normal and inflamed intestinal mucosa selectively inhibit the host immune response and therefore may contribute to the intestinal immune homeostasis.

Original languageEnglish
Pages (from-to)3119-3130
Number of pages12
JournalJournal of Immunology
Volume173
Issue number5
Publication statusPublished - 2004 Sep 1
Externally publishedYes

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Mucous Membrane
T-Lymphocytes
Regulatory T-Lymphocytes
Inflammatory Bowel Diseases
Glucocorticoid-Induced TNFR-Related Protein
Homeostasis
Intestinal Mucosa
Interleukin-10
Intestines
Interleukin-2
Cytokines
Inflammation
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Makita, S., Kanai, T., Oshima, S., Uraushihara, K., Totsuka, T., Sawada, T., ... Watanabe, M. (2004). CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. Journal of Immunology, 173(5), 3119-3130.

CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. / Makita, Shin; Kanai, Takanori; Oshima, Shigeru; Uraushihara, Koji; Totsuka, Teruji; Sawada, Taisuke; Nakamura, Tetsuya; Koganei, Kazutaka; Fukushima, Tsuneo; Watanabe, Mamoru.

In: Journal of Immunology, Vol. 173, No. 5, 01.09.2004, p. 3119-3130.

Research output: Contribution to journalArticle

Makita, S, Kanai, T, Oshima, S, Uraushihara, K, Totsuka, T, Sawada, T, Nakamura, T, Koganei, K, Fukushima, T & Watanabe, M 2004, 'CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells', Journal of Immunology, vol. 173, no. 5, pp. 3119-3130.
Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T et al. CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. Journal of Immunology. 2004 Sep 1;173(5):3119-3130.
Makita, Shin ; Kanai, Takanori ; Oshima, Shigeru ; Uraushihara, Koji ; Totsuka, Teruji ; Sawada, Taisuke ; Nakamura, Tetsuya ; Koganei, Kazutaka ; Fukushima, Tsuneo ; Watanabe, Mamoru. / CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. In: Journal of Immunology. 2004 ; Vol. 173, No. 5. pp. 3119-3130.
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