{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:55:00Z","timestamp":1789606500990,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T00:00:00Z","timestamp":1348185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2012,10]]},"abstract":"Summary<\/jats:title>Background<\/jats:title>Allergen\u2010specific immunotherapy (SIT<\/jats:styled-content>) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD<\/jats:styled-content>4+<\/jats:sup>FOXP<\/jats:styled-content>3+<\/jats:sup> regulatory T cells (Treg cells) are induced during SIT<\/jats:styled-content> in allergic patients. However, the contribution of these cells to SIT<\/jats:styled-content> has not been evaluated in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the in vivo<\/jats:italic> contribution of (i) CD<\/jats:styled-content>4+<\/jats:sup> CD<\/jats:styled-content>25+<\/jats:sup> T cells during SIT<\/jats:styled-content> and of (ii) SIT<\/jats:styled-content>\u2010generated inducible FOXP<\/jats:styled-content>3+<\/jats:sup> Treg cells during allergen exposure to SIT<\/jats:styled-content>\u2010mediated suppression of asthmatic manifestations.<\/jats:p><\/jats:sec>Methods<\/jats:title>We used a mouse model of SIT<\/jats:styled-content> based on the classical OVA<\/jats:styled-content>\u2010driven experimental asthma. Treg cells were quantified by flow cytometry 24 and 96\u00a0h post SIT<\/jats:styled-content> treatment. We depleted CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells prior to SIT<\/jats:styled-content>, and CD<\/jats:styled-content>4+<\/jats:sup>FOXP<\/jats:styled-content>3+<\/jats:sup> T cells prior to allergen challenges to study their contribution to the suppression of allergic manifestations by SIT<\/jats:styled-content> treatment.<\/jats:p><\/jats:sec>Results<\/jats:title>Our data show that depletion of CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells at the time of SIT<\/jats:styled-content> treatment reverses the suppression of airway hyperresponsiveness (AHR<\/jats:styled-content>), but not of airway eosinophilia and specific IgE levels in serum. Interestingly, the number of CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup>FOXP<\/jats:styled-content>3+<\/jats:sup> T cells is transiently increased after SIT<\/jats:styled-content> in the spleen and blood, suggesting the generation of inducible and presumably allergen\u2010specific Treg cells during treatment. Depletion of CD<\/jats:styled-content>4+<\/jats:sup>FOXP<\/jats:styled-content>3+<\/jats:sup> Treg cells after SIT<\/jats:styled-content> treatment partially reverses the SIT<\/jats:styled-content>\u2010induced suppression of airway eosinophilia, but not of AHR<\/jats:styled-content> and serum levels of specific IgE.<\/jats:p><\/jats:sec>Conclusion and clinical relevance<\/jats:title>We conclude that SIT<\/jats:styled-content>\u2010mediated tolerance induction towards AHR<\/jats:styled-content> requires CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup> T cells at the time of allergen injections. In addition, SIT<\/jats:styled-content> generates CD<\/jats:styled-content>4+<\/jats:sup>CD<\/jats:styled-content>25+<\/jats:sup>FOXP<\/jats:styled-content>3+<\/jats:sup> T cells that contribute to the suppression of airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell number or their activity during and after SIT<\/jats:styled-content> could be of clinical relevance to improve the therapeutic effects of SIT<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2222.2012.04064.x","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T10:21:25Z","timestamp":1348222885000},"page":"1519-1528","source":"Crossref","is-referenced-by-count":37,"title":["Contribution of regulatory T<\/scp> cells to alleviation of experimental allergic asthma after specific immunotherapy"],"prefix":"10.1111","volume":"42","author":[{"given":"H.","family":"Maazi","sequence":"first","affiliation":[{"name":"Laboratory of Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, GRIAC Research Institute University Medical Center Groningen (UMCG), University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Shirinbak","sequence":"additional","affiliation":[{"name":"Laboratory of Allergology & Pulmonary Diseases, Department of Pathology & Medical Biology, GRIAC Research Institute University Medical Center Groningen (UMCG), University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Willart","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation University of Ghent Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. M.","family":"Hammad","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoregulation University of Ghent Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cabanski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Boon","sequence":"additional","affiliation":[{"name":"Bioceros B.V. Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology, TWINCORE\/Centre for Experimental and Clinical Infection Research A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz, Centre for Infection Research(HZI) Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Baru","sequence":"additional","affiliation":[{"name":"Institute of Infection Immunology, TWINCORE\/Centre for Experimental and Clinical Infection Research A Joint Venture Between the Medical School Hannover (MHH) and the Helmholtz, Centre for Infection Research(HZI) Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, Allergology and Neonatology, Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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