{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T23:08:07Z","timestamp":1773702487099,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Type 1 regulatory T (Tr1) cells are critical players in maintaining peripheral tolerance, by producing high IL\u201010 levels in association with inducible T\u2010cell co\u2010stimulator (ICOS) expression. Whether these cells play a role in naturally acquired baked egg tolerance is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Evaluate frequencies of egg\u2010responsive Tr1 and Th2 cells in egg\u2010allergic children that naturally acquired baked egg tolerance (BET) versus non\u2010egg\u2010allergic (NEA) children.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells from 70 natural BET and 15 NEA children were stimulated for 7\u2009days with ovalbumin and ovomucoid. By flowcytometry, egg\u2010responsive Tr1 cells were identified by co\u2010expression of CD49b and LAG3, and Th2 cells by expression of CD49b but absence of LAG3. Seven\u2010day cultured supernatant was analyzed for Th1, Th2, Tr1, and Th17 cytokines by MSD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Natural BET children had a higher percentage of egg\u2010responsive Th2 cells vs. NEA children (6.75% vs. 10.35%, <jats:italic>p<\/jats:italic>\u2009=\u2009.006). No significant difference was found in frequencies of egg\u2010responsive Tr1 cells between NEA and natural BET children (11.40% vs. 12.55%, <jats:italic>p<\/jats:italic>\u2009=\u2009.42), although Tr1\u2010related IL\u201010 and IL\u201021 production was higher in BET children. Interestingly, egg\u2010responsive Tr1 cells from NEA children expressed higher ICOS levels vs. natural BET children (97.90 vs. 88.20, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). Supernatant from natural BET children showed elevated levels of Th2 cytokines IL\u20105, IL\u20109 and IL\u201013 and Th17 cytokine IL\u201017A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Natural BET children maintain increased egg\u2010specific Th2 responses, along with comparable proportions of egg\u2010responsive Tr1 cells exhibiting higher IL\u201010 but lower ICOS expression in comparison with NEA children.<\/jats:p><\/jats:sec>","DOI":"10.1111\/pai.70018","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T13:19:47Z","timestamp":1736774387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Egg allergen\u2010specific T\u2010cell and cytokine responses in healthy and egg\u2010allergic children naturally tolerating baked egg"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-0676","authenticated-orcid":false,"given":"Liselot","family":"De Vlieger","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Allergy and Immunology Research Group KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-2249","authenticated-orcid":false,"given":"Lisa","family":"Nuyttens","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Allergy and Immunology Research Group KU Leuven  Leuven Belgium"},{"name":"Department of Pediatrics University Hospitals Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheyenne","family":"Keppens","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation, Allergy and Immunology Research Group KU 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