{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:14:46Z","timestamp":1793412886597,"version":"4.5.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG AG060110"],"award-info":[{"award-number":["R01 AG AG060110"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01 AG009740"],"award-info":[{"award-number":["U01 AG009740"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Though T-cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T-cell subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the United States. We evaluated the counts of T-cell subsets including total, CD4+, and CD8+ T cells and their na\u00efve (Tn), effector memory (Tem), and effector subsets, in the context of age, sex, and exposure to cytomegalovirus (CMV) infection among 8 848 Health and Retirement Study participants, a nationally representative study of adults older than 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV-seropositive and CMV-seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV-seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T-cell subsets by age and sex in a national sample of US adults older than the age of 55 years. Understanding T-cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.<\/jats:p>","DOI":"10.1093\/gerona\/glab300","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T11:08:58Z","timestamp":1633950538000},"page":"927-933","source":"Crossref","is-referenced-by-count":48,"title":["Age-Related Differences in T-Cell Subsets in a Nationally Representative Sample of People Older Than Age 55: Findings From the Health and Retirement Study"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-6985","authenticated-orcid":false,"given":"Bharat","family":"Thyagarajan","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-6478","authenticated-orcid":false,"given":"Jessica","family":"Faul","sequence":"additional","affiliation":[{"name":"Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sithara","family":"Vivek","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung K","family":"Kim","sequence":"additional","affiliation":[{"name":"Davis School of Gerontology, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janko","family":"Nikolich-\u017dugich","sequence":"additional","affiliation":[{"name":"Department of Immunobiology and the University of Arizona Center on Aging, University of Arizona College of Medicine\u2014Tucson, Tucson, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Weir","sequence":"additional","affiliation":[{"name":"Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M","family":"Crimmins","sequence":"additional","affiliation":[{"name":"Davis School of Gerontology, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"2022050521201231100_CIT0001","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1016\/j.vaccine.2010.03.035","article-title":"Ageing and immunity: addressing immune senescence to ensure healthy ageing","volume":"28","author":"Boraschi","year":"2010","journal-title":"Vaccine"},{"key":"2022050521201231100_CIT0002","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/ni.2588","article-title":"Understanding immunosenescence to improve responses to vaccines","volume":"14","author":"Goronzy","year":"2013","journal-title":"Nat Immunol"},{"key":"2022050521201231100_CIT0003","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1126\/science.273.5271.70","article-title":"The aging immune system: primer and prospectus","volume":"273","author":"Miller","year":"1996","journal-title":"Science"},{"key":"2022050521201231100_CIT0004","first-page":"168","article-title":"Establishment of adult peripheral blood lymphocyte subset reference range for an Asian population by single-platform flow cytometry: influence of age, sex, and race and comparison with other published studies","volume":"11","author":"Chng","year":"2004","journal-title":"Clin Diagn Lab Immunol"},{"key":"2022050521201231100_CIT0005","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000337051","article-title":"Influence of age, gender and lifestyle in lymphocyte subsets: report from the Spanish Gait-2 Study","volume":"127","author":"Garcia-Dabrio","year":"2012","journal-title":"Acta Haematol"},{"key":"2022050521201231100_CIT0006","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s11427-009-0086-4","article-title":"Reference ranges and age-related changes of peripheral blood lymphocyte subsets in Chinese healthy adults","volume":"52","author":"Jiao","year":"2009","journal-title":"Sci China C Life Sci"},{"key":"2022050521201231100_CIT0007","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/cyto.b.21234","article-title":"Reference intervals for leukocyte subsets in adults: results from a population-based study using 10-color flow cytometry","volume":"88","author":"Melzer","year":"2015","journal-title":"Cytometry B Clin Cytom"},{"key":"2022050521201231100_CIT0008","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1128\/CVI.00378-08","article-title":"Establishment of reference values of CD4 and CD8 lymphocyte subsets in healthy Nigerian adults","volume":"16","author":"Oladepo","year":"2009","journal-title":"Clin Vaccine Immunol"},{"key":"2022050521201231100_CIT0009","doi-asserted-by":"crossref","first-page":"848","DOI":"10.18632\/aging.100894","article-title":"Aging of immune system: immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults","volume":"8","author":"Qin","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"2022050521201231100_CIT0010","first-page":"959","article-title":"Peripheral blood lymphocyte subsets in adolescents: a longitudinal analysis from the REACH project","volume":"9","author":"Rudy","year":"2002","journal-title":"Clin Diagn Lab Immunol"},{"key":"2022050521201231100_CIT0011","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1128\/CVI.00476-12","article-title":"Reference ranges for lymphocyte subsets among healthy Hong Kong Chinese adults by single-platform flow cytometry","volume":"20","author":"Wong","year":"2013","journal-title":"Clin Vaccine Immunol"},{"key":"2022050521201231100_CIT0012","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.4049\/jimmunol.1301721","article-title":"Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans","volume":"192","author":"Wertheimer","year":"2014","journal-title":"J Immunol"},{"key":"2022050521201231100_CIT0013","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.exger.2016.02.005","article-title":"Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: a systematic review","volume":"77","author":"Weltevrede","year":"2016","journal-title":"Exp Gerontol"},{"key":"2022050521201231100_CIT0014","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1742-4933-10-20","article-title":"Sex, gender and immunosenescence: a key to understand the different lifespan between men and women?","volume":"10","author":"Caruso","year":"2013","journal-title":"Immun Ageing"},{"key":"2022050521201231100_CIT0015","doi-asserted-by":"crossref","DOI":"10.7826\/ISR-UM.06.585031.001.05.0001.1995","volume-title":"Technical Description of the Health and Retirement Study Sample Design","author":"Heeringa","year":"1995"},{"key":"2022050521201231100_CIT0016","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.2307\/146277","article-title":"An overview of the Health and Retirement Study","volume":"30","author":"Juster","year":"1995","journal-title":"J Hum Resour"},{"key":"2022050521201231100_CIT0017","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1093\/ije\/dyu067","article-title":"Cohort profile: the Health and Retirement Study (HRS)","volume":"43","author":"Sonnega","year":"2014","journal-title":"Int J Epidemiol"},{"key":"2022050521201231100_CIT0018","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nri3158","article-title":"Standardizing immunophenotyping for the Human Immunology Project","volume":"12","author":"Maecker","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"2022050521201231100_CIT0019","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jim.2018.09.007","article-title":"Effect of delayed cell processing and cryopreservation on immunophenotyping in multicenter population studies","volume":"463","author":"Thyagarajan","year":"2018","journal-title":"J Immunol Methods"},{"key":"2022050521201231100_CIT0020","volume-title":"Venous Blood Collection and Assay Protocol in the 2016 Health and Retirement Study","author":"Crimmins","year":"2017"},{"key":"2022050521201231100_CIT0021","doi-asserted-by":"crossref","first-page":"8759","DOI":"10.1038\/s41598-020-65016-x","article-title":"Validation of a hybrid approach to standardize immunophenotyping analysis in large population studies: the Health and Retirement Study","volume":"10","author":"Hunter-Schlichting","year":"2020","journal-title":"Sci Rep"},{"key":"2022050521201231100_CIT0022","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10522-017-9739-z","article-title":"Immune parameters associated with mortality in the elderly are context-dependent: lessons from Sweden, Holland and Belgium","volume":"19","author":"Pawelec","year":"2018","journal-title":"Biogerontology"},{"key":"2022050521201231100_CIT0023","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s10522-008-9138-6","article-title":"The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20\u2013100 years of age","volume":"9","author":"Wikby","year":"2008","journal-title":"Biogerontology"},{"key":"2022050521201231100_CIT0024","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1111\/j.1365-2249.2008.03785.x","article-title":"Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals","volume":"155","author":"Chidrawar","year":"2009","journal-title":"Clin Exp Immunol"},{"key":"2022050521201231100_CIT0025","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1742-4933-8-2","article-title":"Differential effects of age, cytomegalovirus-seropositivity and end-stage renal disease (ESRD) on circulating T lymphocyte subsets","volume":"8","author":"Litjens","year":"2011","journal-title":"Immun Ageing"},{"key":"2022050521201231100_CIT0026","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1128\/JVI.79.6.3675-3683.2005","article-title":"Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons","volume":"79","author":"Almanzar","year":"2005","journal-title":"J Virol"},{"key":"2022050521201231100_CIT0027","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s11357-012-9425-7","article-title":"Lower proportion of naive peripheral CD8+ T cells and an unopposed pro-inflammatory response to human cytomegalovirus proteins in vitro are associated with longer survival in very elderly people","volume":"35","author":"Derhovanessian","year":"2013","journal-title":"Age (Dordr)"},{"key":"2022050521201231100_CIT0028","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nri2959","article-title":"Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?","volume":"11","author":"Akbar","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"2022050521201231100_CIT0029","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.yexmp.2005.11.004","article-title":"Inflammation markers predicting frailty and mortality in the elderly","volume":"80","author":"De Martinis","year":"2006","journal-title":"Exp Mol Pathol"},{"key":"2022050521201231100_CIT0030","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.molmed.2007.01.005","article-title":"Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease","volume":"13","author":"Vallejo","year":"2007","journal-title":"Trends Mol Med"},{"key":"2022050521201231100_CIT0031","first-page":"1","article-title":"Immunologic changes in frail older adults","volume":"9","author":"Wang","year":"2014","journal-title":"Transl Med UniSa"},{"key":"2022050521201231100_CIT0032","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1128\/JVI.02425-12","article-title":"Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system","volume":"87","author":"Alonso Arias","year":"2013","journal-title":"J Virol"},{"key":"2022050521201231100_CIT0033","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.cyto.2012.03.013","article-title":"The relationship of cytomegalovirus (CMV) infection with circulatory IFN-alpha levels and IL-7 receptor alpha expression on CD8+ T cells in human aging","volume":"58","author":"Lee","year":"2012","journal-title":"Cytokine"},{"key":"2022050521201231100_CIT0034","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1365-2567.2010.03386.x","article-title":"Cytomegalovirus infection induces the accumulation of short-lived, multifunctional CD4+ CD45RA+ CD27+ T cells: the potential involvement of interleukin-7 in this process","volume":"132","author":"Libri","year":"2011","journal-title":"Immunology"},{"key":"2022050521201231100_CIT0035","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.humimm.2006.10.019","article-title":"Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly","volume":"68","author":"Weinberger","year":"2007","journal-title":"Hum Immunol"},{"key":"2022050521201231100_CIT0036","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4049\/jimmunol.173.1.673","article-title":"Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine","volume":"173","author":"Kang","year":"2004","journal-title":"J Immunol"},{"key":"2022050521201231100_CIT0037","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.mad.2005.11.001","article-title":"Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment","volume":"127","author":"Saule","year":"2006","journal-title":"Mech Ageing Dev"},{"key":"2022050521201231100_CIT0038","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/nm1295-1279","article-title":"Genetic control of the CD4\/CD8 T-cell ratio in humans","volume":"1","author":"Amadori","year":"1995","journal-title":"Nat Med"},{"key":"2022050521201231100_CIT0039","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fimmu.2019.00180","article-title":"Sex differences in older adults\u2019 immune responses to seasonal influenza vaccination","volume":"10","author":"Voigt","year":"2019","journal-title":"Front Immunol"},{"key":"2022050521201231100_CIT0040","doi-asserted-by":"crossref","first-page":"e16103","DOI":"10.1371\/journal.pone.0016103","article-title":"Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States","volume":"6","author":"Simanek","year":"2011","journal-title":"PLoS One"},{"key":"2022050521201231100_CIT0041","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1210\/jcem-64-1-32","article-title":"Influence of testosterone therapy on clinical and immunological features of autoimmune diseases associated with Klinefelter\u2019s syndrome","volume":"64","author":"Bizzarro","year":"1987","journal-title":"J Clin Endocrinol Metab"},{"key":"2022050521201231100_CIT0042","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/0024-3205(94)00508-7","article-title":"Immune cell circulating subsets are affected by gonadal function","volume":"54","author":"Giglio","year":"1994","journal-title":"Life Sci"},{"key":"2022050521201231100_CIT0043","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1046\/j.1365-2249.2000.01329.x","article-title":"The effect of testosterone replacement treatment on immunological features of patients with Klinefelter\u2019s syndrome","volume":"121","author":"Kocar","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"2022050521201231100_CIT0044","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jri.2004.02.001","article-title":"Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women","volume":"63","author":"Kumru","year":"2004","journal-title":"J Reprod Immunol"},{"key":"2022050521201231100_CIT0045","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0531-5565(00)00195-9","article-title":"Immune effects of hormone replacement therapy in post-menopausal women","volume":"36","author":"Porter","year":"2001","journal-title":"Exp Gerontol"},{"key":"2022050521201231100_CIT0046","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1742-4933-10-16","article-title":"Immunosenescence and gender: a study in healthy Cubans","volume":"10","author":"Garcia Verdecia","year":"2013","journal-title":"Immun Ageing"},{"key":"2022050521201231100_CIT0047","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-4933-7-4","article-title":"The effect of ageing on human lymphocyte subsets: comparison of males and females","volume":"7","author":"Yan","year":"2010","journal-title":"Immun Ageing"},{"key":"2022050521201231100_CIT0048","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10522-015-9563-2","article-title":"Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study","volume":"16","author":"Di Benedetto","year":"2015","journal-title":"Biogerontology"},{"key":"2022050521201231100_CIT0049","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/gerona\/glu018","article-title":"CD4:8 ratio &gt;5 is associated with a dominant naive T-cell phenotype and impaired physical functioning in CMV-seropositive very elderly people: results from the BELFRAIL study","volume":"70","author":"Adriaensen","year":"2015","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2022050521201231100_CIT0050","first-page":"1155","article-title":"CD4:8 ratio above 5 is associated with all-cause mortality in CMV-seronegative very old women: results from the BELFRAIL study","volume":"72","author":"Adriaensen","year":"2017","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"2022050521201231100_CIT0051","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1146\/annurev.immunol.22.012703.104702","article-title":"Central memory and effector memory T cell subsets: function, generation, and maintenance","volume":"22","author":"Sallusto","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"2022050521201231100_CIT0052","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/cyto.a.20643","article-title":"Phenotype and function of human T lymphocyte subsets: consensus and issues","volume":"73","author":"Appay","year":"2008","journal-title":"Cytometry A"},{"key":"2022050521201231100_CIT0053","doi-asserted-by":"crossref","first-page":"ofy211","DOI":"10.1093\/ofid\/ofy211","article-title":"Should sex be considered an effect modifier in the evaluation of influenza vaccine effectiveness?","volume":"5","author":"Chambers","year":"2018","journal-title":"Open Forum Infect Dis"}],"container-title":["The Journals of Gerontology: Series A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/biomedgerontology\/advance-article-pdf\/doi\/10.1093\/gerona\/glab300\/41068929\/glab300.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/77\/5\/927\/43552091\/glab300.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article-pdf\/77\/5\/927\/43552091\/glab300.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T17:30:35Z","timestamp":1651771835000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biomedgerontology\/article\/77\/5\/927\/6388164"}},"subtitle":[],"editor":[{"given":"David","family":"Le Couteur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10,11]]},"published-print":{"date-parts":[[2022,5,5]]}},"URL":"https:\/\/doi.org\/10.1093\/gerona\/glab300","relation":{},"ISSN":["1079-5006","1758-535X"],"issn-type":[{"value":"1079-5006","type":"print"},{"value":"1758-535X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,1]]},"published":{"date-parts":[[2021,10,11]]}}}