{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:09:12Z","timestamp":1787508552672,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Regulatory T\u2010cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP\u2010compatible protocol for expanding sorted thymus\u2010derived CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    CD127\n                    <jats:sup>\u2013<\/jats:sup>\n                    (Tregs) as well as CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>+<\/jats:sup>\n                    CD127\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD45RA\n                    <jats:sup>+<\/jats:sup>\n                    (RA\n                    <jats:sup>+<\/jats:sup>\n                    Tregs) cells. We aimed to understand whether thymic RA\n                    <jats:sup>+<\/jats:sup>\n                    Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA\n                    <jats:sup>+<\/jats:sup>\n                    Tregs. We show that both Tregs and RA\n                    <jats:sup>+<\/jats:sup>\n                    Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN\u2010\u03b3 producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA\n                    <jats:sup>+<\/jats:sup>\n                    Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048949","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T13:49:22Z","timestamp":1620222562000},"page":"2086-2092","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Isolation and expansion of thymus\u2010derived regulatory T cells for use in pediatric heart transplant patients"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6089-5828","authenticated-orcid":false,"given":"Marco","family":"Romano","sequence":"first","affiliation":[{"name":"MRC Centre for Transplantation School of Immunology and Microbial Sciences King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Sen","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation School of Immunology and Microbial Sciences King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3942-5201","authenticated-orcid":false,"given":"Cristiano","family":"Scott\u00e0","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation School of Immunology and Microbial Sciences King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowa Y.","family":"Alhabbab","sequence":"additional","affiliation":[{"name":"Applied Medical Sciences Department Division of Immunology King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Rico\u2010Armada","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology and Transplant Cardiology Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I.","family":"Lechler","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation School of Immunology and Microbial Sciences King's College London Guy's Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Burch","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology and Transplant Cardiology Great Ormond Street Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Lombardi","sequence":"additional","affiliation":[{"name":"MRC Centre for Transplantation School of Immunology and Microbial Sciences King's College 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