{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:28:01Z","timestamp":1791646081844,"version":"4.3.4"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012014","name":"Kieikai Research Foundation","doi-asserted-by":"publisher","award":["2017S063"],"award-info":[{"award-number":["2017S063"]}],"id":[{"id":"10.13039\/501100012014","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26292065"],"award-info":[{"award-number":["26292065"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Meiji Holdings Co., Ltd."},{"name":"Meiji Holdings Co., Ltd"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Impaired expansion, stability, and function of regulatory T cells (Tregs) are reported in patients with severe allergy. Transfer of Tregs is a potential means of treating severe food allergy; however, methods to obtain allergen-specific Tregs with stable regulatory activities are needed. To achieve our goal, we examined the characteristics of allergen-specific Tregs by comparing two mouse strains transgenic for the ovalbumin (OVA)-specific T cell receptor gene: Rag23\u22123 and RagD10 mice (OVA23\u22123 and DO11.10 crossed with <jats:italic>Rag2<\/jats:italic> knockout mice, respectively). RagD10 is a tolerant model, whereas Rag23\u22123 shows severe allergy when fed egg white (EW). To examine the differentiation of CD4<jats:sup>+<\/jats:sup> T cells into Foxp3<jats:sup>+<\/jats:sup> Tregs (induced Tregs; iTregs), CD4<jats:sup>+<\/jats:sup> T cells or whole cells from mesenteric lymph nodes or spleens were cultured under Treg-polarization conditions and stimulated with either a combination of anti-CD3 and anti-CD28 antibodies or OVA plus antigen-presenting cells. After stimulation with the antibodies, iTregs were induced at comparable levels from CD4<jats:sup>+<\/jats:sup> T cells from untreated Rag23\u22123 and RagD10 mice. Transfer of the resultant iTregs from untreated Rag23\u22123 mice suppressed allergic responses in EW-fed Rag23\u22123 mice. In contrast, stimulation with OVA plus antigen-presenting cells prevented the differentiation of iTregs from CD4<jats:sup>+<\/jats:sup> T cells from untreated Rag23\u22123 mice, suggesting that OVA-induced T-cell receptor signaling inhibits effective Treg differentiation. Furthermore, antibody-mediated differentiation afforded significantly more iTregs differentiation of na\u00efve (CD44<jats:sup>lo<\/jats:sup>CD62L<jats:sup>hi<\/jats:sup>) CD4<jats:sup>+<\/jats:sup> T cells than of effector\/effector memory (CD44<jats:sup>hi<\/jats:sup>CD62L<jats:sup>lo<\/jats:sup>) T cells isolated from the mesenteric lymph nodes of EW-fed Rag-23\u20133 mice. Excessive production of interleukin-4 and interferon-gamma by CD4<jats:sup>+<\/jats:sup> T cells from EW-fed Rag23\u22123 mice significantly inhibited Treg induction in RagD10 mice, suggesting the severe allergic cytokine milieu likely prevents their differentiation. However, our study showed that allergen-specific Tregs with regulatory activity can be obtained from na\u00efve CD4<jats:sup>+<\/jats:sup> T cells from the intestinal immune system of mice even with severe allergy.<\/jats:p>","DOI":"10.1371\/journal.pone.0324105","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T17:54:16Z","timestamp":1748627656000},"page":"e0324105","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ovalbumin-specific regulatory T cells differentiated from the na\u00efve phenotype (CD44loCD62Lhi) in mesenteric lymph nodes stably suppress enteropathy even in severe food-allergic mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Kyoko","family":"Shibahara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Nishitsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Soga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyo","family":"Bamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hachimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2008-2501","authenticated-orcid":true,"given":"Haruyo","family":"Nakajima-Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"issue":"4","key":"pone.0324105.ref001","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/pai.13443","article-title":"Update on food allergy","volume":"32","author":"RL Peters","year":"2021","journal-title":"Pediatr Allergy Immunol"},{"key":"pone.0324105.ref002","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jaci.2017.11.003","article-title":"Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention, and management. 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