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

Clinical and Experimental Immunology - Tập 140 Số 3 - Trang 540-546 - 2005
Randal K. Gregg1, Christopher M. Smith2, Fiona Clark2, Debbie Dunnion2, Naeem Khan2, Ronjon Chakraverty2, Laxman Nayak3, Paul Moss2
1Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK
2Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, and
3Centre for Applied Gerontology, University of Birmingham, Edgbaston, Birmingham, UK

Tóm tắt

SummaryAgeing 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.

Từ khóa


Tài liệu tham khảo

Nagami, 1984, Ageing and tuberculosis, Gerontology, 30, 308, 10.1159/000212650

McElhaney, 1998, Responses to influenza vaccination in different T cell subsets: a comparison of healthy young and older adults, Vaccine, 6, 1742, 10.1016/S0264-410X(98)00133-9

Douek, 1998, Changes in thymic function with age and during the treatment of HIV infection, Nature, 396, 690, 10.1038/25374

Haynes, 2000, The role of the thymus in immune reconstitution in aging, bone marrow transplantation and HIV-1 infection, Ann Rev Immunol, 18, 529, 10.1146/annurev.immunol.18.1.529

Jameson, 2002, Maintaining the norm: T cell homeostasis, Nat Rev Immunol, 2, 547, 10.1038/nri853

Khan, 2002, Cytomegalovirus seropositivity drives the CD8 T cell repertoire towards greater clonality in healthy elderly individuals, J Immunol, 15, 169:

Globerson, 2000, Ageing of lymphocytes and lymphocytes in the aged, Immunol Today, 21, 515, 10.1016/S0167-5699(00)01714-X

Sakaguchi, 1995, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chain (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases, J Immunol, 155, 1151, 10.4049/jimmunol.155.3.1151

Maloy, 2001, Regulatory T cells in the control of immune pathology, Nat Immunol, 2, 816, 10.1038/ni0901-816

Shevach, 2000, Regulatory T cells in autoimmunity, Ann Rev Immunol, 18, 423, 10.1146/annurev.immunol.18.1.423

Baecher-Allan, 2001, CD4+CD25high regulatory cells in human peripheral blood, J Immunol, 167, 1245, 10.4049/jimmunol.167.3.1245

Jonuleit, 2001, Identification and functional characterization of human CD4(+) CD25(+) T cells with regulatory properties isolated from peripheral blood, J Exp Med, 193, 1285, 10.1084/jem.193.11.1285

Dieckmann, 2001, Ex vivo isolation and characterization of CD4(+) CD25(+) T cells with regulatory properties from human blood, J Exp Med, 193, 1303, 10.1084/jem.193.11.1303

Jonuleit, 2002, Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells, J Exp Med, 196, 255, 10.1084/jem.20020394

Ng, 2001, Human CD4+CD25+ cells: a naturally occurring population of regulatory T cells, Blood, 98, 2736, 10.1182/blood.V98.9.2736

Wing, 2002, Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood, Immunol, 106, 190, 10.1046/j.1365-2567.2002.01412.x

Globerson, 1995, T lymphocytes and aging, Int Arch Allergy Immunol, 107, 491, 10.1159/000237091

Jonuleit, 2000, Induction of interleukin-10 producing, non-proliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells, J Exp Med, 192, 1213, 10.1084/jem.192.9.1213

Levings, 2001, IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells, J Immunol, 166, 5530, 10.4049/jimmunol.166.9.5530

Apostolou, 2002, Origin of regulatory T cells with known specificity for antigen, Nat Immunol, 3, 756, 10.1038/ni816

Bluestone, 2003, Natural versus adaptive regulatory T cells, Nat Rev Immunol, 3, 253, 10.1038/nri1032

Von Boehmer, 2003, Dynamics of suppressor T cells: in vivo veritas, J Exp Med, 198, 845, 10.1084/jem.20031358

Walker, 2003, Antigen-dependent proliferation of CD4+CD25+ regulatory T cells in vivo, J Exp Med, 198, 249, 10.1084/jem.20030315

Fisson, 2003, Continuous activation of autoreactive CD4+CD25+ regulatory T cells in the steady state, J Exp Med, 198, 7373, 10.1084/jem.20030686

Sadeghi, 1999, Phenotypic and functional characteristics of circulating monocytes of elderly persons, Exp Gerontol, 34, 959, 10.1016/S0531-5565(99)00065-0

Castle, 1999, Age-related impaired proliferation of peripheral blood mononuclear cells is associated with increases in both IL10 and IL12, Exp Gerontol, 34, 243, 10.1016/S0531-5565(98)00064-3

Thông tin
Thông tin xuất bản

Clinical and Experimental Immunology

Tập 140 Số 3

540-546

Thông tin tác giả