TY - JOUR
T1 - The number of human peripheral blood CD4+ CD²⁵high regulatory T cells increases with age
AU - Gregg, R
AU - Smith, CM
AU - Clark, Fiona
AU - Dunnion, DJ
AU - Khan, Naeem
AU - Chakraverty, Ronjon
AU - Nayak, Uppinangady
AU - Moss, Paul
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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(+) CD25(high) 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(+) CD25(high) 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(+) CD25(high) 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(+) CD25(high) 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.
AB - 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(+) CD25(high) 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(+) CD25(high) 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(+) CD25(high) 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(+) CD25(high) 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.
KW - ageing
KW - regulatory T cell
UR - http://www.scopus.com/inward/record.url?scp=20444497416&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2005.02798.x
DO - 10.1111/j.1365-2249.2005.02798.x
M3 - Article
C2 - 15932517
SN - 1365-2249
VL - 140
SP - 540
EP - 546
JO - Clinical & Experimental Immunology
JF - Clinical & Experimental Immunology
ER -