Developmental Stage, Phenotype, and Migration Distinguish Naive- and Effector/Memory-like CD4 ⁺ Regulatory T Cells

Abstract

Regulatory T cells (Tregs) fulfill a central role in immune regulation. We reported previously that the integrin α _Eβ 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.