Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors

Marcin L Pekalski, Ricardo C Ferreira, Richard M R Coulson, Antony J Cutler, Hui Guo, Deborah J Smyth, Kate Downes, Calliope A Dendrou, Xaquin Castro Dopico, Laura Esposito, Gillian Coleman, Helen E Stevens, Sarah Nutland, Neil M Walker, Catherine Guy, David B Dunger, Chris Wallace, Timothy I M Tree, John A Todd, Linda S Wicker

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2554-66
Number of pages13
JournalJournal of Immunology
Volume190
Issue number6
DOIs
Publication statusPublished - 15 Mar 2013

Keywords

  • Young Adult
  • Age Factors
  • Humans
  • Cell Differentiation
  • Child
  • Receptors, Interleukin-2
  • Protein Binding
  • CD4-Positive T-Lymphocytes
  • Cell Aging
  • Cells, Cultured
  • Thymus Gland
  • Adult
  • Cell Death
  • Interleukin-2 Receptor alpha Subunit
  • Immunophenotyping

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