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

S Makita, T Kanai, S Oshima, K Uraushihara… - The Journal of …, 2004 - journals.aai.org
S Makita, T Kanai, S Oshima, K Uraushihara, T Totsuka, T Sawada, T Nakamura, K Koganei…
The Journal of Immunology, 2004journals.aai.org
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 …
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+ CD25 bright) suppressed the proliferation and various cytokine productions of CD4+ CD25− T cells. LP CD4+ CD25 bright T cells by themselves produced fewer amounts of IL-2, IFN-γ, and IL-10. Interestingly, LP CD4+ CD25 bright T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4+ CD25 bright 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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