{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:56:38Z","timestamp":1793642198069,"version":"4.5.1"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,1,22]],"date-time":"2020-01-22T00:00:00Z","timestamp":1579651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002975","name":"Dainippon Sumitomo Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002975","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["JP19gm5010001"],"award-info":[{"award-number":["JP19gm5010001"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"iPS Cell Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acquired immune function shows recognizable changes over time with organismal aging. These changes include T-cell dysfunction, which may underlie diminished resistance to infection and possibly various chronic age-associated diseases in the elderly. T-cell dysfunction may occur at distinct stages, from naive cells to the end stages of differentiation during immune responses. The thymus, which generates naive T cells, shows unusually early involution resulting in progressive reduction of T-cell output after adolescence, but peripheral T-cell numbers are maintained through antigen-independent homeostatic proliferation of naive T cells driven by the major histocompatibility complex associated with self-peptides and homeostatic cytokines, retaining the diverse repertoire. However, extensive homeostatic proliferation may lead to the emergence of dysfunctional CD4+ T cells with features resembling senescent cells, termed senescence-associated T (SA-T) cells, which increase and accumulate with age. In situations such as chronic viral infection, T-cell dysfunction may also develop via persistent antigen stimulation, termed exhaustion, preventing possible immunopathology due to excessive immune responses. Exhausted T cells are developed through the effects of checkpoint receptors such as PD-1 and may be reversed with the receptor blockade. Of note, although defective in their regular T-cell antigen-receptor-mediated proliferation, SA-T cells secrete abundant pro-inflammatory factors such as osteopontin, reminiscent of an SA-secretory phenotype. A series of experiments in mouse models indicated that SA-T cells are involved in systemic autoimmunity as well as chronic tissue inflammation following tissue stresses. In this review, we discuss the physiological aspects of T-cell dysfunction associated with aging and its potential pathological involvement in age-associated diseases and possibly cancer.<\/jats:p>","DOI":"10.1093\/intimm\/dxaa006","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T07:43:28Z","timestamp":1579592608000},"page":"223-231","source":"Crossref","is-referenced-by-count":120,"title":["Physiology and pathology of T-cell aging"],"prefix":"10.1093","volume":"32","author":[{"given":"Nagahiro","family":"Minato","sequence":"first","affiliation":[{"name":"Medical Innovation Center, Graduate School of Medicine , Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Hattori","sequence":"additional","affiliation":[{"name":"Medical Innovation Center, Graduate School of Medicine , Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Hamazaki","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Center for iPS Research and Application, Kyoto University , Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,22]]},"reference":[{"key":"2023120103511508900_CIT0001","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fmed.2018.00061","article-title":"The continuum of aging and age-related diseases: common mechanisms but different rates","volume":"5","author":"Franceschi","year":"2018","journal-title":"Front. 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