CD4⁺CD25^bright T cells in human intestinal lamina propria as regulatory cells

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.