Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/11305
Título: Differentiation of human thymic regulatory T cells at the double positive stage
Autor: Nunes-Cabaço, Helena
Caramalho, Íris
Sepúlveda, Nuno
Sousa, Ana E.
Palavras-chave: FOXP3
Human T-cell development
Treg cells
Thymus
Data: 2011
Editora: WILEY-VCH Verlag
Citação: Eur. J. Immunol. 2011. 41: 3604–3614
Resumo: Treg 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.
Descrição: © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Peer review: yes
URI: http://hdl.handle.net/10451/11305
DOI: http://dx.doi.org/10.1002/eji.201141614
ISSN: 0014-2980
Versão do Editor: The definitive version is available at http://onlinelibrary.wiley.com/
Aparece nas colecções:IMM - Artigos em Revistas Internacionais
FM-LIC - Artigos em Revistas Internacionais

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