title: CD4+ CD25+ CD62+ T-regulatory cell subset has optimal suppressive and proliferative potential.
abstract: 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.
authors.affiliation: Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Fu
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.forename: Xia
authors.initials: X
authors.lastname: Mao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Minwei
authors.initials: M
authors.lastname: Mao
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Ding
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bromberg
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D002469:Cell Separation; D054415:Chemokine CCL19; D018932:Chemokine CCL2 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D003092:Colitis; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D005756:Gastritis; D019041:L-Selectin / Q000096:biosynthesis*; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010641:Phenotype; D011409:Propylene Glycols / Q000378:metabolism; D054390:Receptors, CCR2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015704:CD4 Antigens; C515461:Ccl19 protein, mouse; C515335:Ccr2 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D019742:Chemokines, CC; D016207:Cytokines; D011409:Propylene Glycols; D054390:Receptors, CCR2; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D019041:L-Selectin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine