CD4⁺ CD25⁺ CD62⁺ T-Regulatory Cell Subset Has Optimal Suppressive and Proliferative Potential

CD4⁺ CD25⁺ regulatory T cells (Treg) are potent suppressors, and play important roles in autoimmunity and transplantation. Recent reports suggest that CD4⁺ CD25⁺ Treg are not a homogeneous cell population, but the differences in phenotype, function, and mechanisms among different subsets are unknown. Here, we demonstrate CD4 ⁺ CD25⁺ Treg cells can be divided into subsets according to cell-surface expression of CD62L. While both subsets express foxp3 and are anergic, the CD62L⁺ population is more potent on a per cell basis, and proliferates and maintains suppressive function far better than the CD62L- population and unseparated CD4⁺ CD25⁺ Treg. The CD62L ⁺ population preferentially migrates to CCL19, MCP-1 and FTY720. Both CD62L⁺ and CD62L- subsets prevent the development of autoimmune gastritis and colitis induced by CD4⁺ CD25-CD45RB^high cells in severe combined immunodeficiency (SCID) mice. Overall, these results suggest CD4⁺ CD25⁺ Treg are not a homogenous cell population, but can be divided into at least two subsets according to CD62L expression. The CD62L⁺ subset is a more potent suppressor than the CD62L- population or unfractionated CD4⁺ CD25⁺ Treg cells, can be expanded far more easily in culture, and is more responsive to chemokine-driven migration to secondary lymphoid organs. These properties may have significant implications for the clinical manipulation of the CD4 ⁺ CD25⁺ CD62L⁺ cells.