{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:27:32Z","timestamp":1773818852531,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T00:00:00Z","timestamp":1344988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council"},{"DOI":"10.13039\/501100000762","name":"Imperial College Healthcare NHS Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000762","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,11]]},"abstract":"The 2009\/10 pandemic (pH<\/jats:styled-content>1N<\/jats:styled-content>1) highlighted the need for vaccines conferring heterosubtypic immunity against antigenically shifted influenza strains. Although cross\u2010reactive T<\/jats:styled-content> cells are strong candidates for mediating heterosubtypic immunity, little is known about the population\u2010level prevalence, frequency, and cytokine\u2010secretion profile of heterosubtypic T<\/jats:styled-content> cells to pH<\/jats:styled-content>1N<\/jats:styled-content>1. To assess this, pH<\/jats:styled-content>1N<\/jats:styled-content>1 sero\u2010negative adults were recruited. Single\u2010cell IFN<\/jats:styled-content>\u2010\u03b3 and IL<\/jats:styled-content>\u20102 cytokine\u2010secretion profiles to internal proteins of pH<\/jats:styled-content>1N<\/jats:styled-content>1 or live virus were enumerated and characterised. Heterosubtypic T<\/jats:styled-content> cells recognising pH<\/jats:styled-content>1N<\/jats:styled-content>1 core proteins were widely prevalent, being detected in 90% (30 of 33) of pH<\/jats:styled-content>1N<\/jats:styled-content>1\u2010na\u00efve individuals. Although the last exposure to influenza was greater than 6 months ago, the frequency and proportion of the IFN<\/jats:styled-content>\u2010\u03b3\u2010only\u2010secreting T<\/jats:styled-content>\u2010cell subset was significantly higher than the IL<\/jats:styled-content>\u20102\u2010only\u2010secreting subset. CD<\/jats:styled-content>8+<\/jats:sup> IFN<\/jats:styled-content>\u2010\u03b3\u2010only\u2010secreting heterosubtypic T<\/jats:styled-content> cells were predominantly CCR<\/jats:styled-content>7\u2212<\/jats:sup>CD<\/jats:styled-content>45RA<\/jats:styled-content>\u2212<\/jats:sup> effector\u2010memory phenotype, expressing the tissue\u2010homing receptor CXCR<\/jats:styled-content>3 and degranulation marker CD<\/jats:styled-content>107. Receipt of the 2008\u201309 influenza vaccine did not alter the frequency of these heterosubtypic T<\/jats:styled-content> cells, highlighting the inability of current vaccines to maintain this heterosubtypic T<\/jats:styled-content>\u2010cell pool. The surprisingly high prevalence of pre\u2010existing circulating pH<\/jats:styled-content>1N<\/jats:styled-content>1\u2010specific CD<\/jats:styled-content>8+<\/jats:sup> IFN<\/jats:styled-content>\u2010\u03b3\u2010only\u2010secreting effector memory T<\/jats:styled-content> cells with cytotoxic and lung\u2010homing potential in pH<\/jats:styled-content>1N<\/jats:styled-content>1\u2010seronegative adults may partly explain the low case fatality rate despite high rates of infection of the pandemic in young adults.<\/jats:p>","DOI":"10.1002\/eji.201242504","type":"journal-article","created":{"date-parts":[[2012,7,10]],"date-time":"2012-07-10T09:42:19Z","timestamp":1341913339000},"page":"2913-2924","source":"Crossref","is-referenced-by-count":31,"title":["Predominance of heterosubtypic IFN<\/scp>\u2010\u03b3\u2010only\u2010secreting effector memory T<\/scp> cells in pandemic H<\/scp>1N<\/scp>1 naive adults"],"prefix":"10.1002","volume":"42","author":[{"given":"Saranya","family":"Sridhar","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaima","family":"Begom","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Bermingham","sequence":"additional","affiliation":[{"name":"Respiratory Virus Unit Centre for Infections Health protection Agency London"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thedi","family":"Ziegler","sequence":"additional","affiliation":[{"name":"National Institute for Health and Welfare (THL) National Influenza Centre Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Infections Department of Virology National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy S.","family":"Barclay","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Infections Department of Virology National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Openshaw","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajit","family":"Lalvani","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine National Heart and Lung Institute Imperial College London Paddington London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,15]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"279","article-title":"WHO position paper on influenza vaccines","volume":"33","author":"World Health Organization","year":"2005","journal-title":"Wkly Epidemiol Record"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0903810"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/498980"},{"key":"e_1_2_7_5_1","first-page":"297","article-title":"The effect of a previous attack of A1 influenza on susceptibility to A2 virus during the 1957 outbreak","volume":"20","author":"Slepushkin A. 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