Expression of the integrin αEβ7 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 αEβ7, which recognizes epithelial cadherin, identifies the most potent subpopulation of regulatory CD25+ T cells. Strikingly, CD25-negative αE+CD4+ T cells displayed regulatory activity. Both αE+ 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 αE+CD25+ T cells produce almost no cytokines, αE+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 αEβ7 can be regarded as a novel marker for subsets of highly potent, functionally distinct regulatory T cells specialized for crosstalk with epithelial environments.