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

R Gregg, CM Smith, FJ Clark, D Dunnion… - Clinical & …, 2005 - academic.oup.com
R Gregg, CM Smith, FJ Clark, D Dunnion, N Khan, R Chakraverty, L Nayak, PA Moss
Clinical & Experimental Immunology, 2005academic.oup.com
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 …
Summary
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.
Oxford University Press