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Little is known about how cell markers harnessed for T\u2010cell\u2010directed therapy can change with time and upon activation in CeD and other autoimmune conditions. In\u2010depth characterization of gluten\u2010specific CD4<jats:sup>+<\/jats:sup> T cells and CeD\u2010associated (CD38<jats:sup>+<\/jats:sup> and CD103<jats:sup>+<\/jats:sup>) CD8<jats:sup>+<\/jats:sup> and <jats:italic>\u03b3\u03b4<\/jats:italic><jats:sup>+<\/jats:sup> T cells in blood of treated CeD patients undergoing a 3 day gluten challenge is reported. The phenotypic profile of gluten\u2010specific cells changes profoundly with gluten exposure and the cells adopt the profile of gluten\u2010specific cells in untreated disease (CD147<jats:sup>+<\/jats:sup>, CD70<jats:sup>+<\/jats:sup>, programmed cell death protein 1 (PD\u20101)<jats:sup>+<\/jats:sup>, inducible T\u2010cell costimulator (ICOS)<jats:sup>+<\/jats:sup>, CD28<jats:sup>+<\/jats:sup>, CD95<jats:sup>+<\/jats:sup>, CD38<jats:sup>+<\/jats:sup>, and CD161<jats:sup>+<\/jats:sup>), yet with some markers being unique for day 6 cells (C\u2010X\u2010C chemokine receptor type 6 (CXCR6), CD132, and CD147) and with integrin <jats:italic>\u03b1<\/jats:italic>4<jats:italic>\u03b2<\/jats:italic>7, C\u2010C motif chemokine receptor 9 (CCR9), and CXCR3 being expressed stably at baseline and day 6. Among gluten\u2010specific CD4<jats:sup>+<\/jats:sup> T cells, 52% are CXCR5<jats:sup>+<\/jats:sup> at baseline, perhaps indicative of germinal\u2010center reactions, while on day 6 all are CXCR5<jats:sup>\u2212<\/jats:sup>. Strikingly, the phenotypic profile of gluten\u2010specific CD4<jats:sup>+<\/jats:sup> T cells on day 6 largely overlaps with that of CeD\u2010associated (CD38<jats:sup>+<\/jats:sup> and CD103<jats:sup>+<\/jats:sup>) CD8<jats:sup>+<\/jats:sup> and <jats:italic>\u03b3\u03b4<\/jats:italic><jats:sup>+<\/jats:sup> T cells. The antigen\u2010induced shift in phenotype of CD4<jats:sup>+<\/jats:sup> T cells being shared with other disease\u2010associated T cells is relevant for development of T\u2010cell\u2010directed therapies.<\/jats:p>","DOI":"10.1002\/advs.202102778","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:54:18Z","timestamp":1631098458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pathogenic T Cells in Celiac Disease Change Phenotype on Gluten Challenge: Implications for T\u2010Cell\u2010Directed Therapies"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4049-807X","authenticated-orcid":false,"given":"Asbj\u00f8rn","family":"Christophersen","sequence":"first","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"},{"name":"Department of Rheumatology Dermatology and Infectious Diseases Oslo University Hospital  Oslo 0372 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1012-7526","authenticated-orcid":false,"given":"Stephanie","family":"Z\u00fchlke","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eivind G.","family":"Lund","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omri","family":"Snir","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Dahal\u2010Koirala","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise Fremgaard","family":"Risnes","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo  Oslo 0372 Norway"},{"name":"Department of Immunology Oslo University Hospital  Oslo 0372 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen","family":"Jahnsen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Oslo  Oslo 0450 Norway"},{"name":"Department of Gastroenterology Akershus University Hospital  L\u00f8renskog 1478 Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut E. 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