The number of human peripheral blood CD4+ CD25high regulatory T cells increases with age.
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.
Gregg
R
R
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
Smith
C M
CM
Clark
F J
FJ
Dunnion
D
D
Khan
N
N
Chakraverty
R
R
Nayak
L
L
Moss
P A
PA
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*
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