title: Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors.
abstract: As the thymus involutes with age, the maintenance of peripheral naive T cells in humans becomes strongly dependent on peripheral cell division. However, mechanisms that orchestrate homeostatic division remain unclear. In this study we present evidence that the frequency of naive CD4 T cells that express CD25 (IL-2 receptor α-chain) increases with age on subsets of both CD31(+) and CD31(-) naive CD4 T cells. Analyses of TCR excision circles from sorted subsets indicate that CD25(+) naive CD4 T cells have undergone more rounds of homeostatic proliferation than their CD25(-) counterparts in both the CD31(+) and CD31(-) subsets, indicating that CD25 is a marker of naive CD4 T cells that have preferentially responded to survival signals from self-Ags or cytokines. CD25 expression on CD25(-) naive CD4 T cells can be induced by IL-7 in vitro in the absence of TCR activation. Although CD25(+) naive T cells respond to lower concentrations of IL-2 as compared with their CD25(-) counterparts, IL-2 responsiveness is further increased in CD31(-) naive T cells by their expression of the signaling IL-2 receptor β-chain CD122, forming with common γ-chain functional high-affinity IL-2 receptors. CD25 plays a role during activation: CD25(+) naive T cells stimulated in an APC-dependent manner were shown to produce increased levels of IL-2 as compared with their CD25(-) counterparts. This study establishes CD25(+) naive CD4 T cells, which are further delineated by CD31 expression, as a major functionally distinct immune cell subset in humans that warrants further characterization in health and disease.
authors: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
authors: Marcin L
authors: ML
authors: Pekalski
authors: Ricardo C
authors: RC
authors: Ferreira
authors: Richard M R
authors: RM
authors: Coulson
authors: Antony J
authors: AJ
authors: Cutler
authors: Hui
authors: H
authors: Guo
authors: Deborah J
authors: DJ
authors: Smyth
authors: Kate
authors: K
authors: Downes
authors: Calliope A
authors: CA
authors: Dendrou
authors: Xaquin
authors: X
authors: Castro Dopico
authors: Laura
authors: L
authors: Esposito
authors: Gillian
authors: G
authors: Coleman
authors: Helen E
authors: HE
authors: Stevens
authors: Sarah
authors: S
authors: Nutland
authors: Neil M
authors: NM
authors: Walker
authors: Catherine
authors: C
authors: Guy
authors: David B
authors: DB
authors: Dunger
authors: Chris
authors: C
authors: Wallace
authors: Timothy I M
authors: TI
authors: Tree
authors: John A
authors: JA
authors: Todd
authors: Linda S
authors: LS
authors: Wicker
mesh_terms: D000328:Adult; D000367:Age Factors; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D002648:Child; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2