Expression of the integrin α(E)β(7) identifies unique subsets of CD25(+) as well as CD25(−) regulatory T cells

Regulatory CD25(+)CD4(+) T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin α(E)β(7), which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25(+) T cells. Strikingly, CD25-negative α(E)(+)CD4(+) T cells displayed regulatory activity. Both α(E)(+) subsets, CD25(+) and CD25(−), express CTLA-4, suppress T cell proliferation in vitro, and protect mice from colitis in the severe combined immunodeficient model (SCID) in vivo. Whereas α(E)(+)CD25(+) T cells produce almost no cytokines, α(E)(+)CD25(−) T cells represent a unique subset in which high IL-2, IFN-γ and T helper 2-cytokine production is linked with suppressive function. Thus, the integrin α(E)β(7) can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.