Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery

Detalhes bibliográficos
Autor(a) principal: Paiva, Ricardo S.
Data de Publicação: 2013
Outros Autores: Lino, Andreia C., Bergman, Marie-Louise, Caramalho, Íris, Sousa, Ana E., Zelenay, Santiago, Demengeot, Jocelyne
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/20123
Resumo: © 2013 National Academy of Sciences.
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spelling Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the peripheryToleranceDevelopmentLymphopoiesisPolarization© 2013 National Academy of Sciences.Most Forkhead box P3(+) (Foxp3(+)) CD4 regulatory T cell (Treg) precursors are newly formed thymocytes that acquire Foxp3 expression on antigen encounter in the thymus. Differentiation of Treg, however, can also occur in the periphery. What limits this second layer of self- and nonself-reactive Treg production in physiological conditions remains to be understood. In this work, we tested the hypothesis that, similarly to thymic Treg, the precursors of peripheral Treg are immature T cells. We show that CD4(+)CD8(-)Foxp3(-) thymocytes and recent thymic emigrants (RTEs), contrarily to peripheral naïve mature cells, efficiently differentiate into Treg on transfer into lymphopenic mice. By varying donor and recipient mice and conducting ex vivo assays, we document that the preferential conversion of newly formed T cells does not require intrathymic preactivation, is cell-intrinsic, and correlates with low and high sensitivity to natural inhibitors and inducers of Foxp3 expression, such as IL-6, T-cell receptor triggering, and TGF-β. Finally, ex vivo analysis of human thymocytes and peripheral blood T cells revealed that human RTE and newly developed T cells share an increased potential to acquire a FOXP3(bright)CD25(high) Treg phenotype. Our findings indicating that RTEs are the precursors of Tregs differentiated in the periphery should guide the design of Treg-based therapies.This work was funded by the Portuguese Research Council (FCT)under Grant PTDC/SAU-IMU/113541/2009 (to I.C.), fellowships (to R.S.P., A.C.L., and M.-L.B.), and a contract (to I.C.) and the European Union’s 7th Framework Programme (FP7/2007-2013) under Grant 241447 [Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes (NAIMIT); to J.D.].National Academy of SciencesRepositório da Universidade de LisboaPaiva, Ricardo S.Lino, Andreia C.Bergman, Marie-LouiseCaramalho, ÍrisSousa, Ana E.Zelenay, SantiagoDemengeot, Jocelyne2015-09-23T11:26:19Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/20123engPNAS | April 16, 2013 | vol. 110 | no. 16 | 6494-64990027-8424http://dx.doi.org/10.1073/pnas.1221955110info: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:RCAAP2023-11-08T16:05:13Zoai:repositorio.ul.pt:10451/20123Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:38:12.765808Repositório 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 Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
title Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
spellingShingle Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
Paiva, Ricardo S.
Tolerance
Development
Lymphopoiesis
Polarization
title_short Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
title_full Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
title_fullStr Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
title_full_unstemmed Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
title_sort Recent thymic emigrants are the preferential precursors of regulatory T cells differentiated in the periphery
author Paiva, Ricardo S.
author_facet Paiva, Ricardo S.
Lino, Andreia C.
Bergman, Marie-Louise
Caramalho, Íris
Sousa, Ana E.
Zelenay, Santiago
Demengeot, Jocelyne
author_role author
author2 Lino, Andreia C.
Bergman, Marie-Louise
Caramalho, Íris
Sousa, Ana E.
Zelenay, Santiago
Demengeot, Jocelyne
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Paiva, Ricardo S.
Lino, Andreia C.
Bergman, Marie-Louise
Caramalho, Íris
Sousa, Ana E.
Zelenay, Santiago
Demengeot, Jocelyne
dc.subject.por.fl_str_mv Tolerance
Development
Lymphopoiesis
Polarization
topic Tolerance
Development
Lymphopoiesis
Polarization
description © 2013 National Academy of Sciences.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2015-09-23T11:26:19Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/20123
url http://hdl.handle.net/10451/20123
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PNAS | April 16, 2013 | vol. 110 | no. 16 | 6494-6499
0027-8424
http://dx.doi.org/10.1073/pnas.1221955110
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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