Differentiation of human thymic regulatory T cells at the double positive stage

Detalhes bibliográficos
Autor(a) principal: Nunes-Cabaço, Helena
Data de Publicação: 2011
Outros Autores: Caramalho, Íris, Sepúlveda, Nuno, Sousa, Ana E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/11305
Resumo: © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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spelling Differentiation of human thymic regulatory T cells at the double positive stageFOXP3Human T-cell developmentTreg cellsThymus© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimTreg cells, best identified by the expression of the transcription factor FOXP3, play a crucial role in maintaining self-tolerance. Natural Treg cells constitute an independent thymus-derived T-cell lineage whose developmental program in humans is still ill-defined. Here, we provide evidence of a Treg-cell differentiation pathway at the double positive (DP) stage, prior to commitment to the CD4(+) or CD8(+) lineage, in pediatric thymuses. FOXP3(+) DP cells displayed a functional IL-7 receptor and increased Bcl-2 levels that may protect them from cell death/negative selection, and an activated/suppressive phenotype that was lost as CD4 single positive (SP) cells matured and acquired egress markers. A subpopulation of FOXP3(+) DP thymocytes expressing CD103 likely represents the precursor of FOXP3(+) CD8SP cells, which homogeneously expressed this mucosal-homing molecule. Finally, co-cultures of DP thymocytes with primary thymic epithelial cells and multiple linear regression analyses support that FOXP3(+) SP cells are largely derived from FOXP3(+) DP thymocytes. Overall, our data suggest that human Treg-cell lineage commitment significantly occurs at the DP stage with possible implications for the diversity and autoreactivity of the natural Treg-cell repertoire.This work was supported by grant (PTDC/ SAU-MI/66248/2006) from Fundação para a Ciência e a Tecnologia (FCT) and by Programa Operacional Ciência e Inovação 2010 (POCI2010) to AES. H. N. C. received a scholarship from FCT co-financed by POCI 2010.WILEY-VCH VerlagRepositório da Universidade de LisboaNunes-Cabaço, HelenaCaramalho, ÍrisSepúlveda, NunoSousa, Ana E.2014-06-19T15:46:21Z20112011-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/11305engEur. J. Immunol. 2011. 41: 3604–36140014-2980http://dx.doi.org/10.1002/eji.201141614metadata only accessinfo: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:RCAAP2024-11-20T17:15:28Zoai:repositorio.ul.pt:10451/11305Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T17:15:28Repositório 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 Differentiation of human thymic regulatory T cells at the double positive stage
title Differentiation of human thymic regulatory T cells at the double positive stage
spellingShingle Differentiation of human thymic regulatory T cells at the double positive stage
Nunes-Cabaço, Helena
FOXP3
Human T-cell development
Treg cells
Thymus
title_short Differentiation of human thymic regulatory T cells at the double positive stage
title_full Differentiation of human thymic regulatory T cells at the double positive stage
title_fullStr Differentiation of human thymic regulatory T cells at the double positive stage
title_full_unstemmed Differentiation of human thymic regulatory T cells at the double positive stage
title_sort Differentiation of human thymic regulatory T cells at the double positive stage
author Nunes-Cabaço, Helena
author_facet Nunes-Cabaço, Helena
Caramalho, Íris
Sepúlveda, Nuno
Sousa, Ana E.
author_role author
author2 Caramalho, Íris
Sepúlveda, Nuno
Sousa, Ana E.
author2_role author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Nunes-Cabaço, Helena
Caramalho, Íris
Sepúlveda, Nuno
Sousa, Ana E.
dc.subject.por.fl_str_mv FOXP3
Human T-cell development
Treg cells
Thymus
topic FOXP3
Human T-cell development
Treg cells
Thymus
description © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-01-01T00:00:00Z
2014-06-19T15:46:21Z
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/10451/11305
url http://hdl.handle.net/10451/11305
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Eur. J. Immunol. 2011. 41: 3604–3614
0014-2980
http://dx.doi.org/10.1002/eji.201141614
dc.rights.driver.fl_str_mv metadata only access
info:eu-repo/semantics/openAccess
rights_invalid_str_mv metadata only access
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv WILEY-VCH Verlag
publisher.none.fl_str_mv WILEY-VCH Verlag
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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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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