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Naive and stem cell memory T cell subset recovery reveals opposing reconstitution patterns in CD4 and CD8 T cells in chronic graft vs. host disease

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dc.contributor.authorSoares, Maria Vieira
dc.contributor.authorAzevedo, Rita I.
dc.contributor.authorFerreira, Ines
dc.contributor.authorBucar, Sara
dc.contributor.authorRibeiro, Ana C.
dc.contributor.authorVieira, Ana I. S.
dc.contributor.authorPereira, Paulo N G
dc.contributor.authorRibeiro, Ruy M.
dc.contributor.authorLigeiro, Dario
dc.contributor.authorAlho, Ana Cristina
dc.contributor.authorSampaio Soares, António
dc.contributor.authorCamacho, Nádia
dc.contributor.authorMartins, Carlos
dc.contributor.authorLourenço, Fernanda
dc.contributor.authorMoreno, Raul
dc.contributor.authorRitz, Jerome
dc.contributor.authorLacerda, João
dc.date.accessioned2020-12-03T15:08:36Z
dc.date.available2020-12-03T15:08:36Z
dc.date.issued2019
dc.descriptionCopyright © 2019 Soares, Azevedo, Ferreira, Bucar, Ribeiro, Vieira, Pereira, Ribeiro, Ligeiro, Alho, Soares, Camacho, Martins, Lourenço, Moreno, Ritz and Lacerda. 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.abstractThe success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematological malignancies remains hampered by life-threatening chronic graft vs. host disease (cGVHD). Although multifactorial in nature, cGVHD has been associated with imbalances between effector and regulatory T cells (Treg). To further elucidate this issue, we performed a prospective analysis of patients undergoing unrelated donor allo-HSCT after a reduced intensity conditioning (RIC) regimen containing anti-thymocyte globulin (ATG) and the same GVHD prophylaxis, at a single institution. We studied T cell subset homeostasis over a 24-month follow-up after HSCT in a comparative analysis of patients with and without cGVHD. We also quantified naive and memory T cell subsets, proliferation and expression of the apoptosis-related proteins Bcl-2 and CD95. Finally, we assessed thymic function by T cell receptor excision circle (TREC) quantification and T cell receptor (TCR) diversity by TCRVβ spectratyping. While the total number of conventional CD4 (Tcon) and CD8 T cells was similar between patient groups, Treg were decreased in cGVHD patients. Interestingly, we also observed divergent patterns of Naive and Stem Cell Memory (SCM) subset recovery in Treg and Tcon compared to CD8. Patients with cGVHD showed impaired recovery of Naive and SCM Tcon and Treg, but significantly increased frequencies and absolute numbers of Naive and SCM were observed in the CD8 pool. Markedly increased EMRA CD8 T cells were also noted in cGVHD. Taken together, these results suggest that Naive, SCM and EMRA CD8 play a role in the emergence of cGHVD. Reduced Naive and recent thymic emigrant Tcon and Treg in cGVHD was likely due to impaired thymic output, as it was accompanied by decreased CD4 TREC and TCR diversity. On the other hand, CD8 TCR diversity was similar between patient groups. Furthermore, no correlation was observed between CD8 TREC content and Naive CD8 numbers, suggesting limited thymic production of Naive CD8 T cells in patients after transplant, especially in those developing cGVHD. The mechanisms behind the opposing patterns of CD4 and CD8 subset cell recovery in cGVHD remain elusive, but may be linked to thymic damage associated with the conditioning regimen and/or acute GVHD.pt_PT
dc.description.sponsorshipThis project received funding from: 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) (JFLacerda PI), and UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Immunol. 2019 Mar 6;10:334pt_PT
dc.identifier.doi10.3389/fimmu.2019.00334pt_PT
dc.identifier.eissn1664-3224
dc.identifier.urihttp://hdl.handle.net/10451/45111
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontierspt_PT
dc.relationInstituto de Medicina Molecular
dc.relation.publisherversionhttps://www.frontiersin.org/journals/immunology#pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectNaive T cellpt_PT
dc.subjectT lymphocytept_PT
dc.subjectChronic graft vs. host diseasept_PT
dc.subjectHematopoietic stem cell transplantationpt_PT
dc.subjectImmune reconstitutionpt_PT
dc.subjectStem cell memorypt_PT
dc.titleNaive and stem cell memory T cell subset recovery reveals opposing reconstitution patterns in CD4 and CD8 T cells in chronic graft vs. host diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleInstituto de Medicina Molecular
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICT%2F0001%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F50005%2F2019/PT
oaire.citation.startPage334pt_PT
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGodinho A.V. D. Soares
person.familyNameAzevedo
person.familyNameFerreira
person.familyNameBucar
person.familyNameVieira
person.familyNamePereira
person.familyNameRibeiro
person.familyNameAlho
person.familyNameSampaio Soares
person.familyNameLacerda
person.givenNameMaria
person.givenNameRita
person.givenNameInes
person.givenNameSara
person.givenNameAna
person.givenNamePaulo N G
person.givenNameRuy Miguel
person.givenNameAna Cristina
person.givenNameAntónio
person.givenNameJoão
person.identifier564538
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person.identifier.ciencia-idF019-DCC5-CBF0
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person.identifier.ciencia-idB51D-C79F-D60C
person.identifier.ciencia-idC817-9D62-CAEF
person.identifier.ciencia-id8E10-EBAC-FC0E
person.identifier.ciencia-id9A15-E40B-738F
person.identifier.ciencia-id7F1F-164E-9201
person.identifier.ciencia-id6412-2B63-2364
person.identifier.orcid0000-0002-6492-2931
person.identifier.orcid0000-0002-5534-1481
person.identifier.orcid0000-0002-8548-5945
person.identifier.orcid0000-0002-0647-3314
person.identifier.orcid0000-0002-4045-3691
person.identifier.orcid0000-0002-0930-0902
person.identifier.orcid0000-0002-3988-8241
person.identifier.orcid0000-0001-8803-3453
person.identifier.orcid0000-0001-7773-2427
person.identifier.orcid0000-0003-1351-2809
person.identifier.ridI-3729-2013
person.identifier.scopus-author-id7203087102
person.identifier.scopus-author-id55954739900
person.identifier.scopus-author-id8518489600
person.identifier.scopus-author-id36447793000
person.identifier.scopus-author-id57117470800
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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