Academic Journal
Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients
| العنوان: | Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients |
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| المؤلفون: | Romano, M, Sen, M, Scottà, C, Alhabbab, RY, Rico-Armada, A, Lechler, RI, Burch, M, Lombardi, G |
| بيانات النشر: | Wiley-VCH |
| سنة النشر: | 2021 |
| المجموعة: | Brunel University London: Brunel University Research Archive (BURA) |
| مصطلحات موضوعية: | cell therapy, heart transplant, regulatory T cells, thymus |
| الوصف: | Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. ; Supporting Information is available online at: https://onlinelibrary.wiley.com/doi/10.1002/eji.202048949#support-information-section . ; 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+CD127–CD45RA+ (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. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 2086 - 2092; Print-Electronic |
| اللغة: | English |
| تدمد: | 0014-2980 1521-4141 |
| Relation: | European Journal of Immunology; ORCiD: Marco Romano orcid:0000-0001-6089-5828; ORCiD: Cristiano Scottà orcid:0000-0003-3942-5201; Romano, M. et al. (2021) 'Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients', European Journal of Immunology, 51 (8), pp. 2086 - 2092. doi:10.1002/eji.202048949.; https://bura.brunel.ac.uk/handle/2438/29194; https://doi.org/10.1002/eji.202048949 |
| DOI: | 10.1002/eji.202048949 |
| الاتاحة: | https://bura.brunel.ac.uk/handle/2438/29194 https://doi.org/10.1002/eji.202048949 |
| Rights: | Copyright © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ; https://creativecommons.org/licenses/by/4.0/ ; https://creativecommons.org/licenses/by/4.0/legalcode.en ; The Authors |
| رقم الانضمام: | edsbas.543805F6 |
| قاعدة البيانات: | BASE |
| تدمد: | 00142980 15214141 |
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| DOI: | 10.1002/eji.202048949 |