Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells

Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin alpha(E)beta(7) discriminates distinct subsets of murine CD4(+) regulatory T cells. Use of this marker has now helped to unravel a fundamental dichotomy among regulatory T cells. alpha(E)(-)CD25(+) cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, alpha(E)-positve subsets (CD25(+) and CD25(-)) displayed an effector/memory phenotype expressing high levels of E/P-selectin-binding ligands, multiple adhesion molecules as well as receptors for inflammatory chemokines, allowing efficient migration into inflamed sites. Accordingly, alpha(E)-expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.