{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:27:37Z","timestamp":1791095257882,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T00:00:00Z","timestamp":1353888000000},"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":[[2012,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Surrogate biomarkers of efficacy are needed in support of allergen\u2010specific immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to relate changes in peripheral <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cell responses to clinical efficacy during sublingual immunotherapy (<jats:styled-content style=\"fixed-case\">SLIT<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Allergen\u2010specific CD4<jats:sup>+<\/jats:sup> T cell responses were assessed in peripheral blood mononuclear cells (PBMCs) from 89 grass pollen\u2010allergic individuals enrolled in a double\u2010blind placebo\u2010controlled SLIT study conducted in an allergen exposure chamber (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> NCT00619827). Surface phenotype, proliferative responses, cytokine production and gene expression were analysed in coded samples at baseline, and after 2 and 4\u00a0months of SLIT, in PBMCs after <jats:italic>in vitro<\/jats:italic> allergen stimulation or among MHC class II\/peptide (<jats:styled-content style=\"fixed-case\">pMHCII<\/jats:styled-content>)\u2010tetramer\u2010positive CD4<jats:sup>+<\/jats:sup> T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SLIT induced a 29.3% improvement of the average rhinoconjunctivitis total symptom score in the active group, when compared to the placebo group. In parallel, only minor changes in proportions of CD4<jats:sup>+<\/jats:sup> T cells expressing Th1 (CCR5<jats:sup>+<\/jats:sup>, CXCR3<jats:sup>+<\/jats:sup>), Th2 (CRTh2<jats:sup>+<\/jats:sup>, CCR4<jats:sup>+<\/jats:sup>) and Treg (CD25<jats:sup>+<\/jats:sup>, CD127<jats:sup>\u2010<\/jats:sup>, Foxp3<jats:sup>+<\/jats:sup>) markers were detected. A down\u2010regulation of IL\u20104 and IL\u201010 gene expression and IL\u201010 secretion (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001) were observed, as well as a decrease in the frequency of potential \u201cpro\u2010allergic\u201d CD27<jats:sup>\u2010<\/jats:sup> Th2 cells from patients receiving active tablets (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001), but without any correlation with clinical benefit. <jats:styled-content style=\"fixed-case\">pMHCII<\/jats:styled-content>\u2010tetramer analyses failed to document any major impact in both numbers and polarization of circulating Phl p 1\u2010 and Phl p 5\u2010specific CD4<jats:sup>+<\/jats:sup> T cells, confirming that early clinical improvement during SLIT is not associated with dramatic alterations in T lymphocyte responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion &amp; Clinical Relevance<\/jats:title><jats:p>Changes in patterns of peripheral <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup> T cells are not markers for the early onset of efficacy during <jats:styled-content style=\"fixed-case\">SLIT<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12015","type":"journal-article","created":{"date-parts":[[2012,9,30]],"date-time":"2012-09-30T13:09:08Z","timestamp":1349010548000},"page":"1745-1755","source":"Crossref","is-referenced-by-count":45,"title":["Allergen\u2010specific <scp>CD<\/scp>4<sup>+<\/sup> T cell responses in peripheral blood do not predict the early onset of clinical efficacy during grass pollen sublingual immunotherapy"],"prefix":"10.1111","volume":"42","author":[{"given":"M.","family":"Bonvalet","sequence":"first","affiliation":[{"name":"Stallergenes Antony France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Moussu","sequence":"additional","affiliation":[{"name":"Stallergenes Antony France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Wambre","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ricarte","sequence":"additional","affiliation":[{"name":"Stallergenes Antony France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Horiot","sequence":"additional","affiliation":[{"name":"Stallergenes Antony France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.\u2010C.","family":"Rimaniol","sequence":"additional","affiliation":[{"name":"Stallergenes Antony France"},{"name":"Bertin Pharma Montigny le Bretonneux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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