{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:00:34Z","timestamp":1783180834397,"version":"3.54.6"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013866","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["JP24K02289"],"award-info":[{"award-number":["JP24K02289"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP21fk0108571"],"award-info":[{"award-number":["JP21fk0108571"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP22fk0108569"],"award-info":[{"award-number":["JP22fk0108569"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP23fk0410057"],"award-info":[{"award-number":["JP23fk0410057"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japan Science and Technology Agency (JST) SPRING","award":["JPMJSP2127"],"award-info":[{"award-number":["JPMJSP2127"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Coronavirus disease 2019 (COVID-19) pneumonia is prevalent in the elderly infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the mechanisms underlying its age-dependent pathogenesis remain unclear. In this study, we established a mouse-adapted SARS-CoV-2 strain infected Nr4a3-Tocky mouse model to examine T-cell dynamics associated with disease severity. Nr4a3-Tocky mice allow the analysis of the dynamics and induction of antigen-reactive T cells following antigen recognition\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vivo<\/jats:italic>\n                    using fluorescent Timer protein. SARS-CoV-2-infected adult mice exhibited transient body weight loss and recovery, whereas aged mice developed severe pneumonia. BALF viral RNA was comparable between 1\u20134 days post-inoculation (d.p.i.), but declined in adults at 5 d.p.i. Aged mice displayed stronger inflammation as indicated by scRNA-seq, and higher levels of inflammatory cytokines (TNF-\u03b1, CCL2, CXCL10 and IL-6) in BALF correlated with weight loss. Timer analysis revealed induction of antigen-reactive T cells in the adult lungs at 5 and 8 d.p.i., which inversely correlated with disease severity. Additionally, S-specific IFN-\u03b3\u2009\u207a\u2009CD8\u2009\u207a\u2009T cells were detected at 5 d.p.i. in adults, whereas detection of antigen-specific T cells was delayed in aged mice. These results suggest that the coexistence of age-related lung inflammation and delayed induction of antigen-specific T cells is linked to more severe pneumonia, while earlier T-cell responses are associated with improved viral control and milder disease. In this study, we utilized a novel mouse model enabling characterization of antigen-reactive T cells in the local tissue, and investigated inflammatory responses in the lung together with lung-infiltrating virus-specific T cells, finding the dynamics of these immunological parameters associated with the age of the mice. Our analysis provides new insights into understanding how age-related T-cell dysfunction is associated with the severity of SARS-CoV-2 pneumonia.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013866","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:33:24Z","timestamp":1768415604000},"page":"e1013866","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dynamics of lung-infiltrating virus-specific T cells associated with age-dependent SARS-CoV-2 pneumonia severity"],"prefix":"10.1371","volume":"22","author":[{"given":"Rise","family":"Kurokawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatherine Silas","family":"Mtali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innocent 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