{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:47:22Z","timestamp":1753876042314,"version":"3.41.2"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":101,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biological Sciences Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Strategic Program and Core Capability Grants","award":["BBS\/E\/I\/00007031","BBS\/E\/I\/00007037","BBS\/E\/PI\/230001A"],"award-info":[{"award-number":["BBS\/E\/I\/00007031","BBS\/E\/I\/00007037","BBS\/E\/PI\/230001A"]}]},{"name":"Pirbright Flow Cytometry Facility","award":["BBS\/E\/I\/00007039","BBS\/E\/PI\/23NB0003"],"award-info":[{"award-number":["BBS\/E\/I\/00007039","BBS\/E\/PI\/23NB0003"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103865Z\/14\/Z"],"award-info":[{"award-number":["103865Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["J007439","G1001052"],"award-info":[{"award-number":["J007439","G1001052"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union H2020 Programme","award":["764698"],"award-info":[{"award-number":["764698"]}]},{"DOI":"10.13039\/100009378","name":"Leukemia and Lymphoma Research","doi-asserted-by":"publisher","award":["15012"],"award-info":[{"award-number":["15012"]}],"id":[{"id":"10.13039\/100009378","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tissue-resident memory (TRM) T cells play an important role in protection against respiratory infection but whether this memory is maintained by long-lived or dividing cells remains controversial. To address the rate of division of lung TRM T cells, deuterium-enriched water was administered orally to young pigs to label dividing lymphocytes. T-cell subsets were separated from blood, lymph nodes, and airways [bronchoalveolar lavage (BAL)], the latter comprising almost exclusively TRM. We show that, as in other species, circulating memory T-cell subsets divide more rapidly than na\u00efve T cells. Rates of labelling of memory subsets were similar in blood and lymph nodes, consistent with the rapid and free exchange. Strikingly, the fraction of label in BAL was similar to those in blood\/lymph nodes after 5\u201321 days of labelling, suggesting replacement with recently divided cells, but this was preceded at Day 2 by a phase when labelling was lower in BAL than blood\/lymph node in some memory subsets. Our data exclude long-lived TRM as the source of BAL memory cells leaving three possible hypotheses: blood\/airway exchange, in situ proliferation, or proliferation in the lung interstitium followed by migration to BAL. When considered in the context of other information, we favour the latter interpretation. These results indicate the dynamic nature of memory in the lung and have implications for harnessing immune responses against respiratory pathogens.<\/jats:p>","DOI":"10.1093\/discim\/kyaf007","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T06:16:11Z","timestamp":1744438571000},"source":"Crossref","is-referenced-by-count":0,"title":["Proliferation makes a substantive contribution to the maintenance of airway resident memory T-cell subsets in young pigs"],"prefix":"10.1093","volume":"4","author":[{"given":"Eleni","family":"Vatzia","sequence":"first","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George\u2019s, University of London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3126-1752","authenticated-orcid":false,"given":"Ehsan","family":"Sedaghat-Rostami","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]},{"name":"Section of Immunology, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey , Guilford ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Martini","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basudev","family":"Paudyal","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigid Veronica","family":"Carr","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"McNee","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Chiu","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katy","family":"Moffat","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Becca","family":"Asquith","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Beverley","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Imperial College London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Macallan","sequence":"additional","affiliation":[{"name":"Institute for Infection and Immunity, City St George\u2019s, University of London , London ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elma","family":"Tchilian","sequence":"additional","affiliation":[{"name":"The Pirbright Institute , Pirbright ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"2025052711410832300_CIT0001","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1016\/j.immuni.2013.09.013","article-title":"Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus","volume":"39","author":"Sl\u00fctter","year":"2013","journal-title":"Immunity"},{"key":"2025052711410832300_CIT0002","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1016\/j.immuni.2014.12.007","article-title":"Tissue-resident memory T cells","volume":"41","author":"Schenkel","year":"2014","journal-title":"Immunity"},{"key":"2025052711410832300_CIT0003","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1084\/jem.20040341","article-title":"Rapid turnover of effector-memory CD4(+) T cells in healthy humans","volume":"200","author":"Macallan","year":"2004","journal-title":"J Exp Med"},{"key":"2025052711410832300_CIT0004","doi-asserted-by":"publisher","first-page":"2423","DOI":"10.1172\/JCI28941","article-title":"Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo","volume":"116","author":"Vukmanovic-Stejic","year":"2006","journal-title":"J Clin Invest"},{"key":"2025052711410832300_CIT0005","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"Gattinoni","year":"2017","journal-title":"Nat Med"},{"key":"2025052711410832300_CIT0006","doi-asserted-by":"publisher","first-page":"e2005523","DOI":"10.1371\/journal.pbio.2005523","article-title":"Human TSCM cell dynamics in vivo are compatible with long-lived immunological memory and stemness","volume":"16","author":"Costa Del Amo","year":"2018","journal-title":"PLoS Biol"},{"key":"2025052711410832300_CIT0007","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/nri2236","article-title":"Regulation of immunological homeostasis in the respiratory tract","volume":"8","author":"Holt","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2025052711410832300_CIT0008","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41586-021-03351-3","article-title":"Expansible residence decentralizes immune homeostasis","volume":"592","author":"Wijeyesinghe","year":"2021","journal-title":"Nature"},{"key":"2025052711410832300_CIT0009","doi-asserted-by":"publisher","first-page":"e20200050","DOI":"10.1084\/jem.20200050","article-title":"Longevity and replenishment of human liver-resident memory T cells and mononuclear phagocytes","volume":"217","author":"Pallett","year":"2020","journal-title":"J Exp Med"},{"key":"2025052711410832300_CIT0010","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.coi.2019.05.011","article-title":"Human lung tissue resident memory T cells in health and disease","volume":"59","author":"Snyder","year":"2019","journal-title":"Curr Opin Immunol"},{"key":"2025052711410832300_CIT0011","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.3389\/fimmu.2018.01214","article-title":"Niches for the long-term maintenance of tissue-resident memory T cells","volume":"9","author":"Takamura","year":"2018","journal-title":"Front Immunol"},{"key":"2025052711410832300_CIT0012","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1084\/jem.20190557","article-title":"Interstitial-resident memory CD8(+) T cells sustain frontline epithelial memory in the lung","volume":"216","author":"Takamura","year":"2019","journal-title":"J Exp Med"},{"key":"2025052711410832300_CIT0013","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.cell.2014.10.026","article-title":"Spatial map of human T cell compartmentalization and maintenance over decades of life","volume":"159","author":"Thome","year":"2014","journal-title":"Cell"},{"key":"2025052711410832300_CIT0014","doi-asserted-by":"publisher","first-page":"1181716","DOI":"10.3389\/fimmu.2023.1181716","article-title":"Effect of mucosal adjuvant IL-1\u03b2 on heterotypic immunity in a pig influenza model","volume":"14","author":"Schmidt","year":"2023","journal-title":"Front Immunol"},{"key":"2025052711410832300_CIT0015","doi-asserted-by":"publisher","first-page":"4068","DOI":"10.4049\/jimmunol.1800142","article-title":"Comparison of heterosubtypic protection in ferrets and pigs induced by a single-cycle influenza vaccine","volume":"200","author":"Holzer","year":"2018","journal-title":"J Immunol"},{"key":"2025052711410832300_CIT0016","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1098\/rstb.2001.0997","article-title":"Emergence of influenza A viruses","volume":"356","author":"Webby","year":"2001","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2025052711410832300_CIT0017","doi-asserted-by":"publisher","first-page":"a038737","DOI":"10.1101\/cshperspect.a038737","article-title":"Swine influenza A viruses and the tangled relationship with humans","volume":"11","author":"Anderson","year":"2020","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2025052711410832300_CIT0018","doi-asserted-by":"publisher","first-page":"eabd5758","DOI":"10.1126\/scitranslmed.abd5758","article-title":"Importance of the pig as a human biomedical model","volume":"13","author":"Lunney","year":"2021","journal-title":"Sci Transl Med"},{"key":"2025052711410832300_CIT0019","doi-asserted-by":"publisher","first-page":"689406","DOI":"10.3389\/fgene.2021.689406","article-title":"Reference transcriptomes of porcine peripheral immune cells created through bulk and single-cell RNA sequencing","volume":"12","author":"Herrera-Uribe","year":"2021","journal-title":"Front Genet"},{"key":"2025052711410832300_CIT0020","doi-asserted-by":"publisher","first-page":"652","DOI":"10.4049\/jimmunol.2001086","article-title":"Simultaneous aerosol and intramuscular immunization with influenza vaccine induces powerful protective local T cell and systemic antibody immune responses in pigs","volume":"206","author":"Martini","year":"2021","journal-title":"J Immunol"},{"key":"2025052711410832300_CIT0021","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nprot.2014.005","article-title":"Intravascular staining for discrimination of vascular and tissue leukocytes","volume":"9","author":"Anderson","year":"2014","journal-title":"Nat Protoc"},{"key":"2025052711410832300_CIT0022","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.cell.2015.03.031","article-title":"Quantifying memory CD8 T cells reveals regionalization of immunosurveillance","volume":"161","author":"Steinert","year":"2015","journal-title":"Cell"},{"key":"2025052711410832300_CIT0023","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/s41385-021-00478-4","article-title":"Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells","volume":"15","author":"Martini","year":"2022","journal-title":"Mucosal Immunol"},{"key":"2025052711410832300_CIT0024","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.1038\/nprot.2007.420","article-title":"Measurement of cell proliferation by heavy water labeling","volume":"2","author":"Busch","year":"2007","journal-title":"Nat Protoc"},{"key":"2025052711410832300_CIT0025","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/978-1-62703-290-2_10","article-title":"Quantitating lymphocyte homeostasis in vivo in humans using stable isotope tracers","volume":"979","author":"Westera","year":"2013","journal-title":"Methods Mol Biol"},{"key":"2025052711410832300_CIT0026","doi-asserted-by":"publisher","first-page":"4043","DOI":"10.1038\/s41598-017-04404-2","article-title":"Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water","volume":"7","author":"Farthing","year":"2017","journal-title":"Sci Rep"},{"key":"2025052711410832300_CIT0027","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1002\/rcm.328","article-title":"Stable isotopes and the international system of units","volume":"15","author":"Slater","year":"2001","journal-title":"Rapid Commun Mass Spectrom"},{"key":"2025052711410832300_CIT0028","doi-asserted-by":"publisher","first-page":"108501","DOI":"10.1016\/j.celrep.2020.108501","article-title":"CD57(+) memory T cells proliferate in vivo","volume":"33","author":"Ahmed","year":"2020","journal-title":"Cell Rep"},{"key":"2025052711410832300_CIT0029","doi-asserted-by":"publisher","first-page":"111050","DOI":"10.1016\/j.celrep.2022.111050","article-title":"A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs","volume":"40","author":"Gu","year":"2022","journal-title":"Cell Rep"},{"key":"2025052711410832300_CIT0030","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1016\/j.immuni.2023.06.008","article-title":"Site-specific development and progressive maturation of human tissue-resident memory T cells over infancy and childhood","volume":"56","author":"Connors","year":"2023","journal-title":"Immunity"},{"key":"2025052711410832300_CIT0031","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41385-020-0309-3","article-title":"Long-term maintenance of lung resident memory T cells is mediated by persistent antigen","volume":"14","author":"Uddb\u00e4ck","year":"2021","journal-title":"Mucosal Immunol"},{"key":"2025052711410832300_CIT0032","doi-asserted-by":"publisher","first-page":"eaag2031","DOI":"10.1126\/sciimmunol.aag2031","article-title":"Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity","volume":"2","author":"Sl\u00fctter","year":"2017","journal-title":"Sci Immunol"},{"key":"2025052711410832300_CIT0033","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.3389\/fimmu.2018.02054","article-title":"Short lifespans of memory T-cells in bone marrow, blood, and lymph nodes suggest that T-cell memory is maintained by continuous self-renewal of recirculating cells","volume":"9","author":"Baliu-Piqu\u00e9","year":"2018","journal-title":"Front Immunol"},{"key":"2025052711410832300_CIT0034","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1538\/expanim.58.159","article-title":"T cell receptor repertoire in BALB\/c mice varies according to tissue type, sex, age, and hydrocortisone treatment","volume":"58","author":"Kitaura","year":"2009","journal-title":"Exp Anim"},{"key":"2025052711410832300_CIT0035","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13073-021-00918-7","article-title":"Maintenance of the human memory T cell repertoire by subset and tissue site","volume":"13","author":"Miron","year":"2021","journal-title":"Genome Med"},{"key":"2025052711410832300_CIT0036","doi-asserted-by":"publisher","first-page":"537","DOI":"10.4049\/jimmunol.176.1.537","article-title":"Memory T cell populations in the lung airways are maintained by continual recruitment","volume":"176","author":"Ely","year":"2006","journal-title":"J Immunol"},{"key":"2025052711410832300_CIT0037","doi-asserted-by":"publisher","first-page":"4976","DOI":"10.4049\/jimmunol.169.9.4976","article-title":"Long-term maintenance of virus-specific effector memory CD8+ T cells in the lung airways depends on proliferation","volume":"169","author":"Hogan","year":"2002","journal-title":"J Immunol"},{"key":"2025052711410832300_CIT0038","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1084\/jem.20170355","article-title":"The fate and lifespan of human monocyte subsets in steady state and systemic inflammation","volume":"214","author":"Patel","year":"2017","journal-title":"J Exp Med"}],"container-title":["Discovery Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/discovimmunology\/advance-article-pdf\/doi\/10.1093\/discim\/kyaf007\/62917903\/kyaf007.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article-pdf\/4\/1\/kyaf007\/62917903\/kyaf007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article-pdf\/4\/1\/kyaf007\/62917903\/kyaf007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T15:41:16Z","timestamp":1748360476000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article\/doi\/10.1093\/discim\/kyaf007\/8111975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,20]]}},"URL":"https:\/\/doi.org\/10.1093\/discim\/kyaf007","relation":{},"ISSN":["2754-2483"],"issn-type":[{"type":"electronic","value":"2754-2483"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"kyaf007"}}