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Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients

Research output: Contribution to journalArticlepeer-review

Marco Romano, Monica Sen, Cristiano Scottà, Rowa Y. Alhabbab, Andres Rico-Armada, Robert I. Lechler, Michael Burch, Giovanna Lombardi

Original languageEnglish
Pages (from-to)2086-2092
Number of pages7
JournalEuropean Journal of Immunology
Volume51
Issue number8
Early online date25 May 2021
DOIs
Accepted/In press2021
E-pub ahead of print25 May 2021
PublishedAug 2021

Bibliographical note

Funding Information: The authors want to acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St. Thomas’ NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The authors acknowledge Research Councils United Kingdom (RCUK) for the support. This work has been financed by British Heart Foundation (grant TG/16/2/32657). Funding Information: The authors want to acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St. Thomas? NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The authors acknowledge Research Councils United Kingdom (RCUK) for the support. This work has been financed by British Heart Foundation (grant TG/16/2/32657). Publisher Copyright: © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH

King's Authors

Abstract

Regulatory T-cells (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-compatible protocol for expanding sorted thymus-derived CD3+CD4+CD25+CD127 (Tregs) as well as CD3+CD4+CD25+CD127CD45RA+ (RA+Tregs) cells. We aimed to understand whether thymic RA+Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ 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+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.

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