{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:42:44Z","timestamp":1790066564972,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/01615"],"award-info":[{"award-number":["PI16\/01615"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00075"],"award-info":[{"award-number":["PI19\/00075"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","award":["91608878"],"award-info":[{"award-number":["91608878"]}],"id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7\/2007-2011\/259679"],"award-info":[{"award-number":["FP7\/2007-2011\/259679"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejer\u00eda de Transformaci\u00f3n Econ\u00f3mica, Industria, Conocimiento y Universidades. Junta de Andaluc\u00eda","award":["DOC_01421"],"award-info":[{"award-number":["DOC_01421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytomegalovirus (CMV) latent infection and aging contribute to alterations in the function and phenotype of the T-cell pool. We have demonstrated that CMV-seropositivity is associated with the expansion of polyfunctional CD57+ T-cells in young and middle-aged individuals in response to different stimuli. Here, we expand our results on the effects of age and CMV infection on T-cell functionality in a cohort of healthy middle-aged and older individuals stratified by CMV serostatus. Specifically, we studied the polyfunctional responses (degranulation, IFN-\u03b3 and TNF-\u03b1 production) of CD4+, CD8+, CD8+CD56+ (NKT-like), and CD4-CD8- (DN) T-cells according to CD57 expression in response to Staphylococcal Enterotoxin B (SEB). Our results show that CD57 expression by T-cells is not only a hallmark of CMV infection in young individuals but also at older ages. CD57+ T-cells are more polyfunctional than CD57\u2212 T-cells regardless of age. CMV-seronegative individuals have no or a very low percentages of cytotoxic CD4+ T-cells (CD1017a+) and CD4+CD57+ T-cells, supporting the notion that the expansion of these T-cells only occurs in the context of CMV infection. There was a functional shift in T-cells associated with CMV seropositivity, except in the NKT-like subset. Here, we show that the effect of CMV infection and age differ among T-cell subsets and that CMV is the major driving force for the expansion of highly polyfunctional CD57+ T-cells, emphasizing the necessity of considering CMV serology in any study of immunosenescence.<\/jats:p>","DOI":"10.3390\/ijms22189973","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T12:00:44Z","timestamp":1631707244000},"page":"9973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Functional Changes of T-Cell Subsets with Age and CMV Infection"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-7089","authenticated-orcid":false,"given":"Fakhri","family":"Hassouneh","sequence":"first","affiliation":[{"name":"GC01\u2014Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"Department of Internal Medicine II, Centre for Medical Research, University of T\u00fcbingen, 72072 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goldeck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Centre for Medical Research, University of T\u00fcbingen, 72072 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-8996","authenticated-orcid":false,"given":"Alejandra","family":"Pera","sequence":"additional","affiliation":[{"name":"GC01\u2014Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-7748","authenticated-orcid":false,"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, 2333 Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Eline","family":"Slagboom","sequence":"additional","affiliation":[{"name":"Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 Leiden, The Netherlands"},{"name":"Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3600-0163","authenticated-orcid":false,"given":"Graham","family":"Pawelec","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of T\u00fcbingen, 72027 T\u00fcbingen, Germany"},{"name":"Health Sciences North Research Institute, Sudbury, ON P3E 2H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-0295","authenticated-orcid":false,"given":"Rafael","family":"Solana","sequence":"additional","affiliation":[{"name":"GC01\u2014Immunology and Allergy Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, University of C\u00f3rdoba, 14004 Cordoba, Spain"},{"name":"Immunology and Allergy Service, Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/j.jaci.2009.09.017","article-title":"Adaptive immunity","volume":"125","author":"Bonilla","year":"2010","journal-title":"J. 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