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The Journal of Immunology, 2004, 173: 3119-3130.
Copyright © 2004 by The American Association of Immunologists

CD4+CD25bright T Cells in Human Intestinal Lamina Propria as Regulatory Cells1

Shin Makita*, Takanori Kanai2,*, Shigeru Oshima*, Koji Uraushihara*, Teruji Totsuka*, Taisuke Sawada*, Tetsuya Nakamura*, Kazutaka Koganei{dagger}, Tsuneo Fukushima{dagger} and Mamoru Watanabe*

* Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan; and {dagger} Department of Surgery, Yokohama City Hospital, Yokohama, Japan

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+CD25bright 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-{gamma}, 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.




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