title: The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age.
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.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gregg
authors.forename: C M
authors.initials: CM
authors.lastname: Smith
authors.forename: F J
authors.initials: FJ
authors.lastname: Clark
authors.forename: D
authors.initials: D
authors.lastname: Dunnion
authors.forename: N
authors.initials: N
authors.lastname: Khan
authors.forename: R
authors.initials: R
authors.lastname: Chakraverty
authors.forename: L
authors.initials: L
authors.lastname: Nayak
authors.forename: P A
authors.initials: PA
authors.lastname: Moss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count / Q000379:methods; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2