{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:49:35Z","timestamp":1790794175332,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Studies show that proallergic T<jats:sub>H<\/jats:sub>2 cells decrease after successful allergen\u2010specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to exhaustion due to chronic T\u2010cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergen exposure during AIT in mice and two independent patient cohorts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OVA\u2010sensitized C57BL\/6J mice were challenged and treated with OVA, and the development of exhaustion in local and systemic T<jats:sub>H<\/jats:sub>2 cells was analyzed. In patients, the expression of exhaustion\u2010associated surface markers on T<jats:sub>H<\/jats:sub>2 cells was evaluated using flow cytometry in a cross\u2010sectional grass pollen allergy cohort with and without AIT. The treatment effect was further studied in PBMC collected from a prospective long\u2010term AIT cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The exhaustion\u2010associated surface markers CTLA\u20104 and PD\u20101 were significantly upregulated on T<jats:sub>H<\/jats:sub>2 cells upon OVA aerosol exposure in OVA\u2010allergic compared to non\u2010allergic mice. CTLA\u20104 and PD\u20101 decreased after AIT, in particular on the surface of local lung T<jats:sub>H<\/jats:sub>2 cells. Similarly, CTLA\u20104 and PD\u20101 expression was enhanced on T<jats:sub>H<\/jats:sub>2 cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discovered a late\u2010differentiated T<jats:sub>H<\/jats:sub>2 population expressing both markers that decreased during up\u2010dosing but persisted long term during the maintenance phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows that allergen exposure promotes CTLA\u20104 and PD\u20101 expression on T<jats:sub>H<\/jats:sub>2 cells and that the dynamic change in frequencies of exhausted T<jats:sub>H<\/jats:sub>2 cells exhibits a differential pattern during the up\u2010dosing versus the maintenance phases of AIT.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.14896","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T06:21:31Z","timestamp":1620627691000},"page":"2827-2839","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["An exhausted phenotype of T<sub>H<\/sub>2 cells is primed by allergen exposure, but not reinforced by allergen\u2010specific immunotherapy"],"prefix":"10.1111","volume":"76","author":[{"given":"Shu\u2010Hung","family":"Wang","sequence":"first","affiliation":[{"name":"Center of Allergy &amp; Environment (ZAUM) German Research Center for Environmental Health Technical University of Munich and Helmholtz Center Munich Munich Germany"},{"name":"Members of the German Center of Lung Research (DZL) CPC\u2010M Munich Germany"},{"name":"Member of the Helmholtz I&amp;I Initiative Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4826-3419","authenticated-orcid":false,"given":"Ulrich M.","family":"Zissler","sequence":"additional","affiliation":[{"name":"Center of Allergy &amp; Environment (ZAUM) German Research Center for Environmental Health Technical University of Munich and Helmholtz Center Munich Munich Germany"},{"name":"Members of the German Center of Lung Research (DZL) CPC\u2010M Munich 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Research Center for Environmental Health Technical University of Munich and Helmholtz Center Munich Munich Germany"},{"name":"Members of the German Center of Lung Research (DZL) CPC\u2010M Munich Germany"},{"name":"Member of the Helmholtz I&amp;I Initiative Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Kotz","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Medical School Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Pechtold","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Medical School Technical University of Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Kau","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery Medical 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