{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:09:21Z","timestamp":1791227361991,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2012,10,5]],"date-time":"2012-10-05T00:00:00Z","timestamp":1349395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We have observed T helper type 2 (Th2) polarization of systemic immunity in patients with metastatic malignant melanoma. We hypothesized that similar changes in systemic immunity occur with ageing and may be permissive for the development of melanoma. We analysed the peripheral blood of 389 healthy blood donors. All subjects were profiled for peripheral blood T cell and B cell subsets, and 58 of these subjects were profiled for antigen-specific cytotoxic T cell subsets [cytomegalovirus (CMV), influenza and melanoma antigen recognized by T cells 1 (MART-1)]. Ninety-five separate healthy subjects underwent profiling of 42 plasma cytokines. Ageing was associated positively with CD4+CD294+ Th2 cells, and associated negatively with CD3+ T cells, cytotoxic T cells and T helper cells. Ageing was also associated negatively with CMV-, influenza- and MART-1-specific naive and CD8+ T cells. There were significant increases in plasma monocyte chemotactic protein 1 (MCP-1) (CCL1) and regulated upon activation normal T cell expressed and secreted (RANTES) (CCL5) with age. We observed differences in cytokine profiles between males and females; specifically, women had higher levels of sCD40L and PDGF-AA. In summary, we demonstrated in healthy blood donors that ageing was associated with an increase in cellular Th2 bias and a decline in total numbers of T cells. Additionally, there was an increase in MCP-1 and RANTES with ageing. Women had higher levels of sCD40L and PDGF-AA than men.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04644.x","type":"journal-article","created":{"date-parts":[[2012,7,23]],"date-time":"2012-07-23T16:43:09Z","timestamp":1343061789000},"page":"186-193","source":"Crossref","is-referenced-by-count":75,"title":["Normal ageing is associated with an increase in Th2 cells, MCP-1 (CCL1) and RANTES (CCL5), with differences in sCD40L and PDGF-AA between sexes"],"prefix":"10.1093","volume":"170","author":[{"given":"A S","family":"Mansfield","sequence":"first","affiliation":[{"name":"Department of Oncology"},{"name":"Department of Medicine, Division of Hematology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W K","family":"Nevala","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R S","family":"Dronca","sequence":"additional","affiliation":[{"name":"Department of Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A A","family":"Leontovich","sequence":"additional","affiliation":[{"name":"Biomedical Statistics and Informatics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Shuster","sequence":"additional","affiliation":[{"name":"Women's Health Clinic, Division of General Internal Medicine, Mayo Clinic Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S N","family":"Markovic","sequence":"additional","affiliation":[{"name":"Department of Oncology"},{"name":"Department of Medicine, Division of Hematology"},{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,5]]},"reference":[{"key":"2021122708262113200_b1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/0014-4827(65)90211-9","article-title":"The limited in vitro lifetime of human diploid cell strains","volume":"37","author":"Hayflick","year":"1965","journal-title":"Exp Cell Res"},{"key":"2021122708262113200_b2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"Hayflick","year":"1961","journal-title":"Exp Cell Res"},{"key":"2021122708262113200_b3","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cger.2011.07.001","article-title":"Theories and mechanisms of aging","volume":"27","author":"Cefalu","year":"2011","journal-title":"Clin Geriatr Med"},{"key":"2021122708262113200_b4","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1073\/pnas.88.12.5360","article-title":"The aging process: major risk factor for disease and death","volume":"88","author":"Harman","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122708262113200_b5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nature03954","article-title":"Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance","volume":"437","author":"Willimsky","year":"2005","journal-title":"Nature"},{"key":"2021122708262113200_b6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1749-6632.2009.05370.x","article-title":"Potential role of immunosenescence in cancer development","volume":"1197","author":"Fulop","year":"2010","journal-title":"Ann NY Acad Sci"},{"key":"2021122708262113200_b7","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1158\/1078-0432.CCR-08-1980","article-title":"Evidence of systemic Th2-driven chronic inflammation in patients with metastatic melanoma","volume":"15","author":"Nevala","year":"2009","journal-title":"Clin Cancer Res"},{"key":"2021122708262113200_b8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/modpathol.2010.227","article-title":"Regional immunity in melanoma: immunosuppressive changes precede nodal metastasis","volume":"24","author":"Mansfield","year":"2011","journal-title":"Mod Pathol"},{"key":"2021122708262113200_b9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1399-3038.2005.00363.x","article-title":"Age-related changes in intracellular cytokine profiles and Th2 dominance in allergic children","volume":"17","author":"Kawamoto","year":"2006","journal-title":"Pediatr Allergy Immunol"},{"key":"2021122708262113200_b10","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/jid.2010.354","article-title":"Gender differences in melanoma survival: female patients have a decreased risk of metastasis","volume":"131","author":"Joosse","year":"2011","journal-title":"J Invest Dermatol"},{"key":"2021122708262113200_b11","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1073\/pnas.91.9.3652","article-title":"Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant","volume":"91","author":"Carr","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021122708262113200_b12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.coi.2011.05.002","article-title":"CD8+ T cell differentiation in the aging immune system: until the last clone standing","volume":"23","author":"Buchholz","year":"2011","journal-title":"Curr Opin Immunol"},{"key":"2021122708262113200_b13","doi-asserted-by":"crossref","first-page":"e325","DOI":"10.1111\/j.1365-2567.2008.02966.x","article-title":"Induction of copper\/zinc-superoxide dismutase by CCL5\/CCR5 activation causes tumour necrosis factor-alpha and reactive oxygen species production in macrophages","volume":"128","author":"Qiu","year":"2009","journal-title":"Immunology"},{"key":"2021122708262113200_b14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/eji.1830260207","article-title":"CC chemokines induce the generation of killer cells from CD56+ cells","volume":"26","author":"Maghazachi","year":"1996","journal-title":"Eur J Immunol"},{"key":"2021122708262113200_b15","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.4049\/jimmunol.156.6.2095","article-title":"Chemokines and T lymphocyte activation: I. Beta chemokines costimulate human T lymphocyte activation in vitro","volume":"156","author":"Taub","year":"1996","journal-title":"J Immunol"},{"key":"2021122708262113200_b16","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1084\/jem.185.9.1595","article-title":"Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells","volume":"185","author":"Godiska","year":"1997","journal-title":"J Exp Med"},{"key":"2021122708262113200_b17","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.4049\/jimmunol.161.9.5027","article-title":"STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13","volume":"161","author":"Andrew","year":"1998","journal-title":"J Immunol"},{"key":"2021122708262113200_b18","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1084\/jem.184.2.747","article-title":"Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation","volume":"184","author":"Cella","year":"1996","journal-title":"J Exp Med"},{"key":"2021122708262113200_b19","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.4049\/jimmunol.167.7.3765","article-title":"Cytotoxic activity of human dendritic cells is differentially regulated by double-stranded RNA and CD40 ligand","volume":"167","author":"Vidalain","year":"2001","journal-title":"J Immunol"},{"key":"2021122708262113200_b20","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa022600","article-title":"Soluble CD40 ligand in acute coronary syndromes","volume":"348","author":"Heeschen","year":"2003","journal-title":"N Engl J Med"},{"key":"2021122708262113200_b21","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1158\/1078-0432.CCR-0348-03","article-title":"Soluble CD40 ligand plasma levels in lung cancer","volume":"10","author":"Roselli","year":"2004","journal-title":"Clin Cancer Res"},{"key":"2021122708262113200_b22","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1046\/j.1365-2133.1996.d01-1092.x","article-title":"Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo","volume":"135","author":"Barnhill","year":"1996","journal-title":"Br J Dermatol"},{"key":"2021122708262113200_b23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.exger.2007.06.008","article-title":"The immune system in extreme longevity","volume":"43","author":"Sansoni","year":"2008","journal-title":"Exp Gerontol"},{"key":"2021122708262113200_b24","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.mad.2006.01.014","article-title":"Age-dependent modifications of Type 1 and Type 2 cytokines within virgin and memory CD4+ T cells in humans","volume":"127","author":"Alberti","year":"2006","journal-title":"Mech Ageing Dev"},{"key":"2021122708262113200_b25","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/S0531-5565(03)00160-8","article-title":"Marked increase with age of type 1 cytokines within memory and effector\/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence","volume":"38","author":"Zanni","year":"2003","journal-title":"Exp Gerontol"},{"key":"2021122708262113200_b26","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/gerona\/glp198","article-title":"Plasma cytokine levels in a population-based study: relation to age and ethnicity","volume":"65","author":"Stowe","year":"2010","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2021122708262113200_b27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/1479-5876-9-113","article-title":"Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays","volume":"9","author":"Kim","year":"2011","journal-title":"J Transl Med"},{"key":"2021122708262113200_b28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0047-6374(00)00195-0","article-title":"Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians","volume":"121","author":"Gerli","year":"2000","journal-title":"Mech Ageing Dev"},{"key":"2021122708262113200_b29","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1089\/107999099313127","article-title":"Increase in circulating levels of monocyte chemoattractant protein-1 with aging","volume":"19","author":"Inadera","year":"1999","journal-title":"J Interferon Cytokine Res"},{"key":"2021122708262113200_b30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0531-5565(01)00187-5","article-title":"RANTES and MIP-1alpha production by T lymphocytes, monocytes and NK cells from nonagenarian subjects","volume":"37","author":"Mariani","year":"2002","journal-title":"Exp Gerontol"},{"key":"2021122708262113200_b31","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.maturitas.2006.11.002","article-title":"Changes in serum cytokine concentrations during the menopausal transition","volume":"56","author":"Yasui","year":"2007","journal-title":"Maturitas"},{"key":"2021122708262113200_b32","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/00042192-200107000-00008","article-title":"Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy","volume":"8","author":"Deguchi","year":"2001","journal-title":"Menopause"},{"key":"2021122708262113200_b33","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1046\/j.1365-2567.2000.00047.x","article-title":"Sex hormone levels correlate with the activity of cytokine-secreting cells in vivo","volume":"100","author":"Verthelyi","year":"2000","journal-title":"Immunology"},{"key":"2021122708262113200_b34","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0015-0282(00)00622-1","article-title":"Hormone replacement therapy reverses the decrease in natural killer cytotoxicity but does not reverse the decreases in the T-cell subpopulation or interferon-gamma production in postmenopausal women","volume":"74","author":"Yang","year":"2000","journal-title":"Fertil Steril"},{"key":"2021122708262113200_b35","first-page":"513","article-title":"Cytokine production in the bone marrow microenvironment: failure to demonstrate estrogen regulation in early postmenopausal women","volume":"81","author":"Kassem","year":"1996","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2012.04644.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/170\/2\/186\/41907308\/cei4644.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/170\/2\/186\/41907308\/cei4644.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T16:24:12Z","timestamp":1687623852000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/170\/2\/186\/6429091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,5]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,10,5]]},"published-print":{"date-parts":[[2012,10,5]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2012.04644.x","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,11]]},"published":{"date-parts":[[2012,10,5]]}}}