IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| 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/10451/27774 |
Resumo: | Copyright © 2017 Silva, Albuquerque, Matoso, Charmeteau-de-Muylder, Cheynier, Ligeiro, Abecasis, Anjos, Barata, Victorino and Sousa. 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) or licensor 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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IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activityNaive CD4 T-cellsT-cell homeostasisIL-7ThymusThymectomyCopyright © 2017 Silva, Albuquerque, Matoso, Charmeteau-de-Muylder, Cheynier, Ligeiro, Abecasis, Anjos, Barata, Victorino and Sousa. 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) or licensor 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.Naive CD4 T-cell maintenance is critical for immune competence. We investigated here the fine-tuning of homeostatic mechanisms of the naive compartment to counteract the loss of de novo CD4 T-cell generation. Adults thymectomized in early childhood during corrective cardiac surgery were grouped based on presence or absence of thymopoiesis and compared with age-matched controls. We found that the preservation of the CD31− subset was independent of the thymus and that its size is tightly controlled by peripheral mechanisms, including prolonged cell survival as attested by Bcl-2 levels. Conversely, a significant contraction of the CD31+ naive subset was observed in the absence of thymic activity. This was associated with impaired responses of purified naive CD4 T-cells to IL-7, namely, in vitro proliferation and upregulation of CD31 expression, which likely potentiated the decline in recent thymic emigrants. Additionally, we found no apparent constraint in the differentiation of naive cells into the memory compartment in individuals completely lacking thymic activity despite upregulation of DUSP6, a phosphatase associated with increased TCR threshold. Of note, thymectomized individuals featuring some degree of thymopoiesis were able to preserve the size and diversity of the naive CD4 compartment, further arguing against complete thymectomy in infancy. Overall, our data suggest that robust peripheral mechanisms ensure the homeostasis of CD31− naive CD4 pool and point to the requirement of continuous thymic activity to the maintenance of IL-7-driven homeostatic proliferation of CD31+ naive CD4 T-cells, which is essential to secure T-cell diversity throughout life.This work was supported by Fundação para a Ciência e Tecnologia (FCT; POCI2010/IC/83068/2007 to RV; PTDC/SAU-MIC/109786/2009 to AS), and Calouste Gulbenkian Foundation (P132532/2013 to AS). SS, AA, and PM received FCT scholarships.Frontiers MediaRepositório da Universidade de LisboaSilva, Susana L.Albuquerque, Adriana S.Matoso, PaulaCharmeteau-de-Muylder, BénédicteCheynier, RémiLigeiro, DárioAbecasis, MiguelAnjos, RuiBarata, João T.Victorino, Rui M. M.Sousa, Ana E.2017-05-25T11:30:19Z2017-01-192017-01-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/27774engFront. Immunol. January 2017 | Volume 8 | Article 201664-322410.3389/fimmu.2017.00020info: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:RCAAP2023-11-08T16:19:00Zoai:repositorio.ul.pt:10451/27774Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:44:07.598189Repositório 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 |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| title |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| spellingShingle |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity Silva, Susana L. Naive CD4 T-cells T-cell homeostasis IL-7 Thymus Thymectomy |
| title_short |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| title_full |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| title_fullStr |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| title_full_unstemmed |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| title_sort |
IL-7-induced proliferation of human naive CD4 T-cells relies on continued thymic activity |
| author |
Silva, Susana L. |
| author_facet |
Silva, Susana L. Albuquerque, Adriana S. Matoso, Paula Charmeteau-de-Muylder, Bénédicte Cheynier, Rémi Ligeiro, Dário Abecasis, Miguel Anjos, Rui Barata, João T. Victorino, Rui M. M. Sousa, Ana E. |
| author_role |
author |
| author2 |
Albuquerque, Adriana S. Matoso, Paula Charmeteau-de-Muylder, Bénédicte Cheynier, Rémi Ligeiro, Dário Abecasis, Miguel Anjos, Rui Barata, João T. Victorino, Rui M. M. Sousa, Ana E. |
| author2_role |
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 |
Silva, Susana L. Albuquerque, Adriana S. Matoso, Paula Charmeteau-de-Muylder, Bénédicte Cheynier, Rémi Ligeiro, Dário Abecasis, Miguel Anjos, Rui Barata, João T. Victorino, Rui M. M. Sousa, Ana E. |
| dc.subject.por.fl_str_mv |
Naive CD4 T-cells T-cell homeostasis IL-7 Thymus Thymectomy |
| topic |
Naive CD4 T-cells T-cell homeostasis IL-7 Thymus Thymectomy |
| description |
Copyright © 2017 Silva, Albuquerque, Matoso, Charmeteau-de-Muylder, Cheynier, Ligeiro, Abecasis, Anjos, Barata, Victorino and Sousa. 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) or licensor 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 |
2017 |
| dc.date.none.fl_str_mv |
2017-05-25T11:30:19Z 2017-01-19 2017-01-19T00:00:00Z |
| dc.type.status.fl_str_mv |
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/10451/27774 |
| url |
http://hdl.handle.net/10451/27774 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Front. Immunol. January 2017 | Volume 8 | Article 20 1664-3224 10.3389/fimmu.2017.00020 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Frontiers Media |
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Frontiers Media |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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