{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:21:30Z","timestamp":1768339290906,"version":"3.49.0"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,7,11]]},"abstract":"<jats:p>\n            Humoral responses to infection or vaccination require T cell\u2013B cell interactions. T follicular helper (T\n            <jats:sub>FH<\/jats:sub>\n            ) cells drive germinal center (GC) responses by providing help to B cells, whereas T follicular regulatory (T\n            <jats:sub>FR<\/jats:sub>\n            ) cells regulate them. Both mature GC\u2013located T\n            <jats:sub>FH<\/jats:sub>\n            and T\n            <jats:sub>FR<\/jats:sub>\n            cells are widely characterized by the expression of ICOS and PD-1. However, although human T\n            <jats:sub>FR<\/jats:sub>\n            cells share many phenotypic characteristics with T\n            <jats:sub>FH<\/jats:sub>\n            cells, we found that ICOS and PD-1 are up-regulated differently in each. Although T\n            <jats:sub>FH<\/jats:sub>\n            cells express these proteins synchronously during maturation, they define three maturation stages in T\n            <jats:sub>FR<\/jats:sub>\n            cells. T\n            <jats:sub>FR<\/jats:sub>\n            cells in an intermediate maturation stage express ICOS, and it is only at the last stage of differentiation that both molecules are expressed at high levels. Although most T\n            <jats:sub>FR<\/jats:sub>\n            cells within the B cell follicle are PD-1\n            <jats:sup>\u2212<\/jats:sup>\n            , the T\n            <jats:sub>FR<\/jats:sub>\n            within the GC are ICOS\n            <jats:sup>+<\/jats:sup>\n            PD-1\n            <jats:sup>+<\/jats:sup>\n            . These results show that T\n            <jats:sub>FH<\/jats:sub>\n            and T\n            <jats:sub>FR<\/jats:sub>\n            cells within human lymphoid tissue follow distinct maturation stages.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt8901","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T17:58:29Z","timestamp":1752256709000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["PD-1 and ICOS are coexpressed in T follicular helper cells but define three stages of maturation of T follicular regulatory cells"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-3436","authenticated-orcid":true,"given":"Filipa","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal."},{"name":"Faculdade de Medicina, Universidade de Lisboa, Lisboa, 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Lisboa, Portugal."},{"name":"Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany."}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-8500","authenticated-orcid":true,"given":"Luis","family":"Graca","sequence":"additional","affiliation":[{"name":"Gulbenkian Institute for Molecular Medicine, Lisboa, Portugal."},{"name":"Faculdade de Medicina, Universidade de Lisboa, Lisboa, 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