The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age

Clin Exp Immunol. 2005 Jun;140(3):540-6. doi: 10.1111/j.1365-2249.2005.02798.x.

Abstract

Ageing is associated with evidence of immune deficiency and dysregulation. Key changes in the immune system with ageing include a progressive reduction in naive T cell output associated with thymic involution and peripheral expansion of oligoclonal memory T cells. These features are associated with evidence of impaired immune responsiveness both in vitro and in vivo, termed immune senescence. CD4+ CD25+ T cells have recently been recognized as mediators of peripheral immune regulation and play a role in the control of autoimmune and pathogen-specific immune responses. The significance of CD4+ CD25+ regulatory T cells in the context of immunosenescence is not known. We have investigated the number, phenotype and function of CD4+ CD25+ T cells in healthy volunteers over a wide age range. We demonstrate that the number of CD4+ CD25+ and CD4+ CD25high T cells in healthy volunteers increases with age. In both age groups CD4+ CD25+ T cells showed a phenotype consistent with that described for regulatory T cells. Further analysis of CD4+ CD25high T cells in young and elderly donors showed equivalent expression of intracellular CTLA-4 and surface expression of activation markers. In vitro, functional titration assays of CD4+ CD25high T cells demonstrated equivalent regulatory function in both young and elderly donors, with suppression of proliferation and cytokine production in response to polyclonal T cell stimulation. These observations demonstrate an increase in peripheral blood CD4+ CD25high regulatory T cells associated with ageing. The relevance of these expanded cells in relation to the immune senescence seen in the elderly as yet remains unclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigens, CD
  • Antigens, Differentiation / immunology
  • Biomarkers / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cell Division / immunology
  • Cytokines / immunology
  • Humans
  • Immunophenotyping / methods
  • Immunosuppressive Agents / immunology
  • Lymphocyte Activation / immunology
  • Lymphocyte Count / methods
  • Middle Aged
  • Receptors, Interleukin-2 / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Biomarkers
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • Immunosuppressive Agents
  • Receptors, Interleukin-2