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Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seasonal H1N1 influenza A virus (sH1N1)-specific CD4 and CD8 T cells was associated with 28% (95% CI 11%, 41%) and 22% (95% CI 8%, 33%) lower pH1N1 infection odds, respectively. We observed the same associations for individuals with pre-epidemic hemagglutination inhibition (HAI) titers &lt; 40. There was no correlation between pre-existing influenza virus-specific CD4 and CD8 T cell response and HAI titer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We demonstrated homosubtypic and cross-strain protection against influenza infections was associated with T cell response, especially CD4 T cell response. These protections were independent of the protection associated with HAI titer. Therefore, T cell response could be an assessment of individual and population immunity for future epidemics and pandemics, in addition to using HAI titer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-022-02429-7","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T20:02:47Z","timestamp":1658347367000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study"],"prefix":"10.1186","volume":"20","author":[{"given":"Tim K.","family":"Tsang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Tai","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky J.","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy H. 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For participants aged 8 to 17 years, proxy written consent from parents or legal guardians was obtained in addition to their own written assent. The study protocol was approved by the Institutional Review Board of the University of Hong Kong and the Hong Kong Department of Health Ethics Committee (IRB reference number: UW 08-008).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"BJC reports honoraria from AstraZeneca, GlaxoSmithKline, Moderna, Roche, and Sanofi Pasteur. All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"230"}}