Expression of the integrin αEβ₇identifies 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.