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Maturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantation

2020Artigo científico Acesso aberto
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dc.contributor.authorMatos, Tiago R.
dc.contributor.authorHirakawa, Masahiro
dc.contributor.authorAlho, Ana Cristina
dc.contributor.authorNeleman, Lars
dc.contributor.authorGraca, Luis
dc.contributor.authorRitz, Jerome
dc.date.accessioned2021-02-05T18:50:30Z
dc.date.available2021-02-05T18:50:30Z
dc.date.issued2020
dc.descriptionCopyright © 2021 Matos, Hirakawa, Alho, Neleman, Graca and Ritz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.pt_PT
dc.description.abstractCD4+ Regulatory T cells (Treg) play a critical role in maintaining immune homeostasis. Various Treg subsets have been identified, however the heterogeneity of Treg subpopulations during development remains uncharacterized. Using mass cytometry we obtained single cell data on expression of 35 functional markers to examine the heterogeneity of Treg cells at birth and in adults. Unsupervised clustering algorithms FlowSOM and ACCENSE were used to quantify Treg heterogeneity. As expected, Treg in umbilical cord blood were predominately naïve while Treg in adult blood were predominately central memory and effector memory cells. Although umbilical cord blood Treg are mostly naïve cells, we observed multiple phenotypic Treg subsets in cord blood. Nevertheless, peripheral blood in adults contained higher percentages of Treg and the heterogeneity of Treg was significantly increased in adults. We also studied Treg heterogeneity throughout a 2-year period after allogeneic hematopoietic stem cell transplantation (alloHSCT) and in patients with chronic graft-versus-host disease (cGVHD). Treg heterogeneity recovered rapidly after alloHSCT and gradually increased in the first two years post-transplant. However, patients with cGVHD had significantly fewer distinct Treg subpopulations, proposing a correlation between a disrupted Treg heterogeneity and cGVHD. Our study is the first to compare human Treg heterogeneity at birth, in healthy adults and in patients after alloHSCT with and without cGVHD. This approach to characterize Treg heterogeneity based on expression of a large panel of functional markers may enable future studies to identify specific Treg defects that contribute to immune dysfunction.pt_PT
dc.description.sponsorshipThis work was supported by NIH grant P01CA229092, EADV Research Fellowship, Rene-Touraine Fellowship and a generous contribution from the Fundação para a Ciência e a Tecnologia (FCT), FCT SFRH/BD/98980/2013pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Immunol. 2021 Jan 18;11:570550pt_PT
dc.identifier.doi10.3389/fimmu.2020. 570550pt_PT
dc.identifier.eissn1664-3224
dc.identifier.urihttp://hdl.handle.net/10451/46215
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationCPG ODN ADJUVANT TO LOW-DOSE IL-2 AS A NOVEL THERAPY FOR MULTIPLE IMMUNE DISEASES
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectTreg - regulatory T cellpt_PT
dc.subjectImmunologypt_PT
dc.subjectT cellpt_PT
dc.subjectHeterogeneitypt_PT
dc.subjectDiversitypt_PT
dc.subjectGvHDpt_PT
dc.subjectalloHSCTpt_PT
dc.subjectCD4pt_PT
dc.titleMaturation and phenotypic heterogeneity of human CD4+ regulatory T cells from birth to adulthood and after allogeneic stem cell transplantationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberSFRH/BD/98980/2013
oaire.awardTitleCPG ODN ADJUVANT TO LOW-DOSE IL-2 AS A NOVEL THERAPY FOR MULTIPLE IMMUNE DISEASES
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F98980%2F2013/PT
oaire.citation.startPage570550pt_PT
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume11pt_PT
person.familyNameMatos
person.familyNameAlho
person.familyNameSilva Graca
person.givenNameTiago R.
person.givenNameAna Cristina
person.givenNameLuis Ricardo
person.identifier690449
person.identifierB-8887-2008
person.identifier.ciencia-id7F1F-164E-9201
person.identifier.ciencia-id6C19-B162-F561
person.identifier.orcid0000-0003-2864-8207
person.identifier.orcid0000-0001-8803-3453
person.identifier.orcid0000-0001-6935-8500
person.identifier.scopus-author-id57117470800
person.identifier.scopus-author-id36138488700
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication2962860b-b7e5-451c-9d33-ba98d67fd3c3
relation.isAuthorOfPublication7d54b7cc-ae62-4806-98da-556f4731f221
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