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 α(E)β(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. α(E) (−)CD25(+) cells expressed L-selectin and CCR7, enabling recirculation through lymphoid tissues. In contrast, α(E)-positive 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, α(E)-expressing cells were found to be the most potent suppressors of inflammatory processes in disease models such as antigen-induced arthritis.