{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:06:06Z","timestamp":1790676366541,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,1,10]],"date-time":"2016-01-10T00:00:00Z","timestamp":1452384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008903","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008903","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Aging is accompanied by altered T\u2010cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101), in the T cells of aged mice emphasize the importance of investigations into the relationship between T\u2010cell exhaustion and aging\u2010associated immune dysfunction. In this study, we demonstrate that T\u2010cell immunoglobulin mucin domain\u20103 (Tim\u20103), another exhaustion marker, is up\u2010regulated on aged T cells, especially <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells. Tim\u20103\u2010expressing cells also produced <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101, but Tim\u20103<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells had a distinct phenotype that included the expression of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>44 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>62L, from Tim\u20103<jats:sup>\u2212<\/jats:sup><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101<jats:sup>+<\/jats:sup> cells. Tim\u20103<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells showed more evident properties associated with exhaustion than Tim\u20103<jats:sup>\u2212<\/jats:sup><jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells: an exhaustion\u2010related marker expression profile, proliferative defects following homeostatic or <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 and induced normal <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells to produce <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010, which might contribute to immune dysregulation in aged mice. The generation of Tim\u20103\u2010expressing <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>49d and their unbiased <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> V\u03b2 usage. In conclusion, we found that a <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T\u2010cell population with age\u2010associated exhaustion was distinguishable by its expression of Tim\u20103. These results provide clues for understanding the alterations that occur in T\u2010cell populations with age and for improving dysfunctions related to the aging of the immune system.<\/jats:p>","DOI":"10.1111\/acel.12435","type":"journal-article","created":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T04:43:18Z","timestamp":1452487398000},"page":"291-300","source":"Crossref","is-referenced-by-count":124,"title":["Characterization of age\u2010associated exhausted <scp>CD<\/scp>8<sup>+<\/sup> T cells defined by increased expression of Tim\u20103 and <scp>PD<\/scp>\u20101"],"prefix":"10.1111","volume":"15","author":[{"given":"Kyoo\u2010A","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Immunology Research Institute of Pharmaceutical Sciences College of Pharmacy Seoul National University 1 Gwanak\u2010ro, Gwanak\u2010gu Seoul 151\u2010742 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang\u2010Soo","family":"Shin","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Research Institute of Pharmaceutical Sciences College of Pharmacy Seoul National University 1 Gwanak\u2010ro, Gwanak\u2010gu Seoul 151\u2010742 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Science Graduate School of Convergence Science and Technology Seoul National University 1 Gwanak\u2010ro, Gwanak\u2010gu Seoul 151\u2010742 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Chan","family":"Song","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology Research Institute of Pharmaceutical Sciences College of Pharmacy Seoul National University 1 Gwanak\u2010ro, Gwanak\u2010gu Seoul 151\u2010742 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