{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T22:46:49Z","timestamp":1770677209468,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,12,2]],"date-time":"2015-12-02T00:00:00Z","timestamp":1449014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007398","name":"Strategiske Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Det Frie Forskningsr\u00e5d","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>First\u2010born children are at higher risk of developing a range of immune\u2010mediated diseases. The underlying mechanism of \u2018birth\u2010order effects\u2019 on disease risk is largely unknown, but <jats:italic>in utero<\/jats:italic> programming of the child's immune system may play a role.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We studied the association between birth order and the functional response of stimulated cord blood T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Purified cord blood T cells were polyclonally activated with anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>3\u2010\/anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>28\u2010coated beads in a subgroup of 28 children enrolled in the <jats:styled-content style=\"fixed-case\">COPSAC<\/jats:styled-content><jats:sub>2010<\/jats:sub> birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup> T cells were assessed by flow cytometry. Production of <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b3, <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20104, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201013, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 was measured in the supernatants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 secretion (<jats:italic>P<\/jats:italic> = 0.007) and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25 expression on <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> helper T cells (<jats:italic>P<\/jats:italic> = 0.0003) in the activated cord blood T cells were selectively reduced in first\u2010born children, while the percentage of circulating <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup> cord blood T cells was independent of birth order.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>First\u2010born infants display a reduced anti\u2010inflammatory profile in T cells at birth. This possible <jats:italic>in utero<\/jats:italic> \u2018birth\u2010order\u2019 T\u2010cell programming may contribute to later development of immune\u2010mediated diseases by increasing overall immune reactivity in first\u2010born children as compared to younger siblings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12799","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T18:44:13Z","timestamp":1445971453000},"page":"323-332","source":"Crossref","is-referenced-by-count":13,"title":["Divergent response profile in activated cord blood <scp>T<\/scp> cells from first\u2010born child implies birth\u2010order\u2010associated <i>in utero<\/i> immune programming"],"prefix":"10.1111","volume":"71","author":[{"given":"M.","family":"Kragh","sequence":"first","affiliation":[{"name":"Center for Biological Sequence Analysis Department of Systems Biology Technical University of Denmark Lyngby Denmark"}]},{"given":"J. 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M.","family":"Wolsk","sequence":"additional","affiliation":[{"name":"Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}]},{"given":"H.","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital University of Copenhagen Copenhagen Denmark"}]},{"given":"S.","family":"Brix","sequence":"additional","affiliation":[{"name":"Center for Biological Sequence Analysis Department of Systems Biology Technical University of Denmark Lyngby Denmark"}]}],"member":"311","published-online":{"date-parts":[[2015,12,2]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"171","volume-title":"From Birth to Five, A Study Heal. Behav. 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