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Suppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibility

dc.contributor.authorBianchi, Joana
dc.contributor.authorVieira, Ana I. S.
dc.contributor.authorLigeiro, Dário
dc.contributor.authorAzevedo, Rita I.
dc.contributor.authorLacerda, João
dc.date.accessioned2021-05-26T13:31:15Z
dc.date.available2021-05-26T13:31:15Z
dc.date.issued2021
dc.descriptionCopyright © 2021 The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license.pt_PT
dc.description.abstractRegulatory 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.pt_PT
dc.description.sponsorshipThis 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).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationImmunohorizons. 2021 May 12;5(5):307-321pt_PT
dc.identifier.doi10.4049/immunohorizons.2100021pt_PT
dc.identifier.eissn2573-7732
dc.identifier.urihttp://hdl.handle.net/10451/48183
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherThe American Association of Immunologists, Inc.pt_PT
dc.relationFPJ001262pt_PT
dc.relationA DEFINIR
dc.relation.publisherversionhttps://www.immunohorizons.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleSuppression by allogeneic-specific regulatory T cells is dependent on the degree of HLA compatibilitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleA DEFINIR
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F105769%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0001%2F2011/PT
oaire.citation.endPage321pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage307pt_PT
oaire.citation.titleImmunoHorizonspt_PT
oaire.citation.volume5pt_PT
oaire.fundingStreamOE
oaire.fundingStream3599-PPCDT
person.familyNameBianchi
person.familyNameVieira
person.familyNameLigeiro
person.familyNameAzevedo
person.familyNameLacerda
person.givenNameJoana
person.givenNameAna
person.givenNameDário Jose Pirralha
person.givenNameRita
person.givenNameJoão
person.identifier559297
person.identifier.ciencia-idC817-9D62-CAEF
person.identifier.ciencia-id311D-A47D-A6E6
person.identifier.ciencia-id1512-E3F9-5FD4
person.identifier.ciencia-id6412-2B63-2364
person.identifier.orcid0000-0002-1964-547X
person.identifier.orcid0000-0002-4045-3691
person.identifier.orcid0000-0001-5306-3679
person.identifier.orcid0000-0002-5534-1481
person.identifier.orcid0000-0003-1351-2809
person.identifier.scopus-author-id55954739900
person.identifier.scopus-author-id6603819609
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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