{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:50:33Z","timestamp":1793083833454,"version":"4.5.0"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T00:00:00Z","timestamp":1475107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,15]],"date-time":"2016-10-15T00:00:00Z","timestamp":1476489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-\u03b3], tumor necrosis factor alpha [TNF-\u03b1], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i.<jats:italic>Ex vivo<\/jats:italic>flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67<jats:sup>+<\/jats:sup>) CD8<jats:sup>+<\/jats:sup>T cells with an early effector phenotype (perforin<jats:sup>+<\/jats:sup>CD27<jats:sup>+<\/jats:sup>) at day 6 p.i. Low frequencies of influenza virus-specific IFN-\u03b3-producing CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells produced mainly IFN-\u03b3 and\/or TNF-\u03b1, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and<jats:italic>in vitro<\/jats:italic>reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we provide the first detailed characterization of magnitude, kinetics, and phenotype of specific T cells recruited to the lungs of influenza virus-infected pigs, and we could demonstrate multifunctionality, cross-reactivity, and memory formation of these cells. This, and ensuing work in the pig, will strengthen the position of this species as a large-animal model for human influenza virus infection and will immediately benefit vaccine development for improved control of influenza virus infections in pigs.<\/jats:p>","DOI":"10.1128\/jvi.01211-16","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T02:48:46Z","timestamp":1470883726000},"page":"9364-9382","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":63,"title":["Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung"],"prefix":"10.1128","volume":"90","author":[{"given":"Stephanie C.","family":"Talker","sequence":"first","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stadler","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna C.","family":"Koinig","sequence":"additional","affiliation":[{"name":"University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin H.","family":"Mair","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"Rodr\u00edguez-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Graage","sequence":"additional","affiliation":[{"name":"University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Zell","sequence":"additional","affiliation":[{"name":"Department of Virology and Antiviral Therapy, Jena University Hospital, Friedrich Schiller University, Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"D\u00fcrrwald","sequence":"additional","affiliation":[{"name":"Viral Vaccines, Business Unit Animal Health, IDT Biologika GmbH, Dessau-Rosslau, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Starick","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timm","family":"Harder","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Weissenb\u00f6ck","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Forensic Veterinary Medicine, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lamp","sequence":"additional","affiliation":[{"name":"Institute of Virology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine E.","family":"Hammer","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ladinig","sequence":"additional","affiliation":[{"name":"University Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Saalm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Gerner","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1343"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7367-7373.1998"},{"key":"e_1_3_2_4_2","first-page":"158","article-title":"The pig as a mixing vessel for influenza viruses: human and veterinary implications","volume":"3","author":"Ma W","year":"2008","unstructured":"Ma W, Kahn RE, Richt JA. 2008. The pig as a mixing vessel for influenza viruses: human and veterinary implications. J Mol Genet Med 3:158\u2013166.","journal-title":"J Mol Genet Med"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1863-2378.2008.01217.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/512813"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.044974-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2009.131082"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.12.002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ618"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08157"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/zph.12049"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines3010022"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00840-15"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00237"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/273238a0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.4049\/jimmunol.159.11.5197","article-title":"CD8+ T cells clear influenza virus by perforin or Fas-dependent processes","volume":"159","author":"Topham DJ","year":"1997","unstructured":"Topham DJ, Tripp RA, Doherty PC. 1997. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J Immunol 159:5197\u20135200.","journal-title":"J Immunol"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/267354a0"},{"key":"e_1_3_2_19_2","first-page":"417","article-title":"Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo","volume":"58","author":"Taylor PM","year":"1986","unstructured":"Taylor PM, Askonas BA. 1986. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology 58:417\u2013420.","journal-title":"Immunology"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102243"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.09.013"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0313180"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402975"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002381"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501702"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2612"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3350"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7833"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016245"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44675"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.67"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2011.11.002"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(00)00172-3"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2427(01)00342-7"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-82-11-2697"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01211-10"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.10.098"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032400"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.07.033"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2014.06.007"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151922"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502632"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-015-0182-3"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2012.02375.x"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00381-13"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830170912"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2012.06.011"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-008-0244-1"},{"key":"e_1_3_2_49_2","unstructured":"WHO. 2009. Information for laboratory diagnosis of pandemic (H1N1) 2009 virus in humans\u2014revised. National Influenza Centre Shek Kip Mei Kowloon Hong Kong. http:\/\/www.who.int\/csr\/resources\/publications\/swineflu\/WHO_Diagnostic_RecommendationsH1N1_20090521.pdf."},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.02.020"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803903"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05548-11"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2008.06.003"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00308.x"},{"key":"e_1_3_2_55_2","first-page":"578","article-title":"Discrimination between two subsets of porcine CD8+ cytolytic T lymphocytes by the expression of CD5 antigen","volume":"81","author":"Saalm\u00fcller A","year":"1994","unstructured":"Saalm\u00fcller A, Hirt W, Maurer S, Weiland E. 1994. Discrimination between two subsets of porcine CD8+ cytolytic T lymphocytes by the expression of CD5 antigen. Immunology 81:578\u2013583.","journal-title":"Immunology"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.1996.tb00010.x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-44-18"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2013.01.003"},{"key":"e_1_3_2_59_2","first-page":"557","volume-title":"Diseases of swine","author":"van Reeth K","year":"2012","unstructured":"van Reeth K, Brown IH, Olsen CW. 2012. Influenza A virus, p 557\u2013571. In Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW (ed), Diseases of swine, 10th ed. Wiley-Blackwell, Hoboken, NJ.","edition":"10"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1838"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80573-7"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032431"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.09.007"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2274"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.f.1774"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-12-4341"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/80877"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030916"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6377"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102695"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11239-11246.2005"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00688-6"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1051\/vetres\/2010046"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.05.013"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2010.00164.x"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01820-12"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01211-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01211-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T16:35:46Z","timestamp":1692462946000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01211-16"}},"subtitle":[],"editor":[{"given":"S.","family":"Schultz-Cherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10,15]]},"references-count":76,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2016,10,15]]}},"alternative-id":["10.1128\/JVI.01211-16"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01211-16","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,15]]},"assertion":[{"value":"2016-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}