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
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/10451/45111 |
Resumo: | Copyright © 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. |
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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 diseaseNaive T cellT lymphocyteChronic graft vs. host diseaseHematopoietic stem cell transplantationImmune reconstitutionStem cell memoryCopyright © 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.The 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.This 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.FrontiersRepositório da Universidade de LisboaSoares, Maria VieiraAzevedo, Rita I.Ferreira, InesBucar, SaraRibeiro, Ana C.Vieira, Ana I. S.Pereira, Paulo N GRibeiro, Ruy M.Ligeiro, DarioAlho, Ana CristinaSampaio Soares, AntónioCamacho, NádiaMartins, CarlosLourenço, FernandaMoreno, RaulRitz, JeromeLacerda, João2020-12-03T15:08:36Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/45111engFront Immunol. 2019 Mar 6;10:33410.3389/fimmu.2019.003341664-3224info: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:RCAAP2023-11-08T16:46:37Zoai:repositorio.ul.pt:10451/45111Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:57:35.769507Repositório 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 |
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 |
| title |
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 |
| spellingShingle |
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 Soares, Maria Vieira Naive T cell T lymphocyte Chronic graft vs. host disease Hematopoietic stem cell transplantation Immune reconstitution Stem cell memory |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| author |
Soares, Maria Vieira |
| author_facet |
Soares, Maria Vieira Azevedo, Rita I. Ferreira, Ines Bucar, Sara Ribeiro, Ana C. Vieira, Ana I. S. Pereira, Paulo N G Ribeiro, Ruy M. Ligeiro, Dario Alho, Ana Cristina Sampaio Soares, António Camacho, Nádia Martins, Carlos Lourenço, Fernanda Moreno, Raul Ritz, Jerome Lacerda, João |
| author_role |
author |
| author2 |
Azevedo, Rita I. Ferreira, Ines Bucar, Sara Ribeiro, Ana C. Vieira, Ana I. S. Pereira, Paulo N G Ribeiro, Ruy M. Ligeiro, Dario Alho, Ana Cristina Sampaio Soares, António Camacho, Nádia Martins, Carlos Lourenço, Fernanda Moreno, Raul Ritz, Jerome Lacerda, João |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Soares, Maria Vieira Azevedo, Rita I. Ferreira, Ines Bucar, Sara Ribeiro, Ana C. Vieira, Ana I. S. Pereira, Paulo N G Ribeiro, Ruy M. Ligeiro, Dario Alho, Ana Cristina Sampaio Soares, António Camacho, Nádia Martins, Carlos Lourenço, Fernanda Moreno, Raul Ritz, Jerome Lacerda, João |
| dc.subject.por.fl_str_mv |
Naive T cell T lymphocyte Chronic graft vs. host disease Hematopoietic stem cell transplantation Immune reconstitution Stem cell memory |
| topic |
Naive T cell T lymphocyte Chronic graft vs. host disease Hematopoietic stem cell transplantation Immune reconstitution Stem cell memory |
| description |
Copyright © 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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z 2020-12-03T15:08:36Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/45111 |
| url |
http://hdl.handle.net/10451/45111 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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Front Immunol. 2019 Mar 6;10:334 10.3389/fimmu.2019.00334 1664-3224 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Frontiers |
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Frontiers |
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