CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential

Am J Transplant. 2004 Jan;4(1):65-78. doi: 10.1046/j.1600-6143.2003.00293.x.


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-CD45RBhigh 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.

MeSH terms

  • Animals
  • CD4 Antigens / biosynthesis*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Division
  • Cell Movement
  • Cell Separation
  • Chemokine CCL19
  • Chemokine CCL2 / metabolism
  • Chemokines, CC / metabolism
  • Chemotaxis
  • Colitis
  • Cytokines / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Fingolimod Hydrochloride
  • Flow Cytometry
  • Gastritis
  • L-Selectin / biosynthesis*
  • Lymphocyte Subsets
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Phenotype
  • Propylene Glycols / metabolism
  • Receptors, CCR2
  • Receptors, CCR7
  • Receptors, Chemokine / metabolism
  • Receptors, Interleukin-2 / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sphingosine / analogs & derivatives
  • T-Lymphocytes / metabolism*
  • Time Factors


  • CD4 Antigens
  • Ccl19 protein, mouse
  • Ccr2 protein, mouse
  • Ccr7 protein, mouse
  • Chemokine CCL19
  • Chemokine CCL2
  • Chemokines, CC
  • Cytokines
  • Propylene Glycols
  • Receptors, CCR2
  • Receptors, CCR7
  • Receptors, Chemokine
  • Receptors, Interleukin-2
  • L-Selectin
  • Fingolimod Hydrochloride
  • Sphingosine