Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/48183 |
Resumo: | Copyright © 2021 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibilityCopyright © 2021 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license.Regulatory T cell (Treg) infusion for graft-versus-host disease treatment has been increasingly investigated. However, polyclonal Treg may suppress the desired graft-versus-leukemia effect. Although allogeneic-specific (allo-specific) Treg may provide a more-targeted graft-versus-host disease treatment, there is the need to develop easily translatable expansion protocols and to better characterize their specificity and mechanisms of suppression. In this article, we provide a robust protocol for human allo-specific Treg expansion and characterize their phenotype, potency, and specificity of suppression by testing different expansion conditions and suppression assay milieus. We found that higher concentrations of IL-2 during expansion with allogeneic APC yielded allo-specific Treg that were more-potent suppressors and displayed a more activated phenotype. Although responses to the same APC present during expansion were the most suppressed, responses to third-party APC partially matched to the expansion APC were still significantly more suppressed than responses to fully mismatched APC. Furthermore, suppression of responses to the expansion APC was strictly contact dependent, whereas suppression of responses to mismatched APC was partially independent of contact. Finally, distinct subsets in fresh and expanded Treg could be described using multidimensional visualization techniques. We propose that allo-specific Treg are HLA specific and that the mechanisms of suppression elicited depend on their compatibility with the stimulators.This work was supported by Fundação para a Ciência e Tecnologia, Portugal, under the Harvard Medical School–Portugal Program Project Induction of Immune Tolerance in Human Allogeneic Hematopoietic Stem Cell Transplantation (HMSP-ICT/0001/2011) and Gilead Sciences, under Programa Gilead GÉNESE (FPJ001262). J.B. received a Ph.D. grant from Fundação para a Ciência e Tecnologia (PD/BD/105769/2014).The American Association of Immunologists, Inc.Repositório da Universidade de LisboaBianchi, JoanaVieira, Ana I. S.Ligeiro, DárioAzevedo, Rita I.Lacerda, João2021-05-26T13:31:15Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/48183engImmunohorizons. 2021 May 12;5(5):307-32110.4049/immunohorizons.21000212573-7732info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:51:24Zoai:repositorio.ul.pt:10451/48183Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:00:04.660969Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
title |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
spellingShingle |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility Bianchi, Joana |
title_short |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
title_full |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
title_fullStr |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
title_full_unstemmed |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
title_sort |
Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility |
author |
Bianchi, Joana |
author_facet |
Bianchi, Joana Vieira, Ana I. S. Ligeiro, Dário Azevedo, Rita I. Lacerda, João |
author_role |
author |
author2 |
Vieira, Ana I. S. Ligeiro, Dário Azevedo, Rita I. Lacerda, João |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Bianchi, Joana Vieira, Ana I. S. Ligeiro, Dário Azevedo, Rita I. Lacerda, João |
description |
Copyright © 2021 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-05-26T13:31:15Z 2021 2021-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/48183 |
url |
http://hdl.handle.net/10451/48183 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Immunohorizons. 2021 May 12;5(5):307-321 10.4049/immunohorizons.2100021 2573-7732 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
The American Association of Immunologists, Inc. |
publisher.none.fl_str_mv |
The American Association of Immunologists, Inc. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134547867074560 |