{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:19:17Z","timestamp":1791566357334,"version":"4.3.4"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"82","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2023,4,14]]},"abstract":"<jats:p>\n                    The mechanisms by which FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe or vaccine recognition and away from self-reactivity remain incompletely understood. To explore underappreciated heterogeneity in human Tfr cell development, function, and localization, we used paired\n                    <jats:italic>TCRVA<\/jats:italic>\n                    \/\n                    <jats:italic>TCRVB<\/jats:italic>\n                    sequencing to distinguish tonsillar Tfr cells that are clonally related to natural regulatory T cells (nTfr) from those likely induced from T follicular helper (Tfh) cells (iTfr). The proteins iTfr and nTfr cells differentially expressed were used to pinpoint their in situ locations via multiplex microscopy and establish their divergent functional roles. In silico analyses and in vitro tonsil organoid tracking models corroborated the existence of separate T\n                    <jats:sub>reg<\/jats:sub>\n                    -to-nTfr and Tfh-to-iTfr developmental trajectories. Our results identify human iTfr cells as a distinct CD38\n                    <jats:sup>+<\/jats:sup>\n                    , germinal center\u2013resident, Tfh-descended subset that gains suppressive function while retaining the capacity to help B cells, whereas CD38\n                    <jats:sup>\u2212<\/jats:sup>\n                    nTfr cells are elite suppressors primarily localized in follicular mantles. Interventions differentially targeting specific Tfr cell subsets may provide therapeutic opportunities to boost immunity or more precisely treat autoimmune diseases.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.ade8162","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T13:58:06Z","timestamp":1680875886000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":77,"title":["Human T follicular helper clones seed the germinal center\u2013resident regulatory pool"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9228-5896","authenticated-orcid":true,"given":"Carole","family":"Le Coz","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2177-5633","authenticated-orcid":true,"given":"Derek A.","family":"Oldridge","sequence":"additional","affiliation":[{"name":"Center for Computational and Genomic Medicine, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-4050","authenticated-orcid":true,"given":"Ramin S.","family":"Herati","sequence":"additional","affiliation":[{"name":"Department of Medicine, NYU Grossman School of Medicine, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-9059","authenticated-orcid":true,"given":"Nina","family":"De Luna","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-819X","authenticated-orcid":true,"given":"James","family":"Garifallou","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emylette","family":"Cruz Cabrera","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-6938","authenticated-orcid":true,"given":"Jonathan P.","family":"Belman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Pueschl","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa V.","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainsley V.\u00a0C.","family":"Knox","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-8369","authenticated-orcid":true,"given":"Whitney","family":"Reid","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen B.","family":"Zur","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Department of Otolaryngology: Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4102-3615","authenticated-orcid":true,"given":"Steven D.","family":"Handler","sequence":"additional","affiliation":[{"name":"Pediatric Otolaryngology, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Department of Otolaryngology: Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":true,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA."},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 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