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Pre-existing SARS-CoV-2-reactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in childhood. The functional quality of the cross-reactive memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (\u03b2-coronavirus), 229E and NL63 (\u03b1-coronaviruses), rhinovirus, Epstein\u2013Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-\u03b3, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2220320120","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T14:18:06Z","timestamp":1678803486000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":74,"title":["Functional SARS-CoV-2 cross-reactive CD4\n                    <sup>+<\/sup>\n                    T cells established in early childhood decline with age"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-1479","authenticated-orcid":false,"given":"Marion","family":"Humbert","sequence":"first","affiliation":[{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet","place":["Huddinge, Sweden"]},{"name":"Center for 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