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Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models

Our understanding of how thymocytes differentiate into many subtypes has been increased progressively in its complexity. At early life, the thymus provides a suitable microenvironment with specific combination of stromal cells, growth factors, cytokines, and chemokines to induce the bone marrow lymp...

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Autores principales: Belizário, José E., Brandão, Wesley, Rossato, Cristiano, Peron, Jean Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904118/
https://www.ncbi.nlm.nih.gov/pubmed/27313405
http://dx.doi.org/10.1155/2016/9523628
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author Belizário, José E.
Brandão, Wesley
Rossato, Cristiano
Peron, Jean Pierre
author_facet Belizário, José E.
Brandão, Wesley
Rossato, Cristiano
Peron, Jean Pierre
author_sort Belizário, José E.
collection PubMed
description Our understanding of how thymocytes differentiate into many subtypes has been increased progressively in its complexity. At early life, the thymus provides a suitable microenvironment with specific combination of stromal cells, growth factors, cytokines, and chemokines to induce the bone marrow lymphoid progenitor T-cell precursors into single-positive CD4(+) and CD8(+) T effectors and CD4(+)CD25(+) T-regulatory cells (Tregs). At postthymic compartments, the CD4(+) T-cells acquire distinct phenotypes which include the classical T-helper 1 (Th1), T-helper 2 (Th2), T-helper 9 (Th9), T-helper 17 (Th17), follicular helper T-cell (Tfh), and induced T-regulatory cells (iTregs), such as the regulatory type 1 cells (Tr1) and transforming growth factor-β- (TGF-β-) producing CD4(+) T-cells (Th3). Tregs represent only a small fraction, 5–10% in mice and 1-2% in humans, of the overall CD4(+) T-cells in lymphoid tissues but are essential for immunoregulatory circuits mediating the inhibition and expansion of all lineages of T-cells. In this paper, we first provide an overview of the major cell-intrinsic developmental programs that regulate T-cell lineage fates in thymus and periphery. Next, we introduce the SV40 immortomouse as a relevant mice model for implementation of new approaches to investigate thymus organogenesis, CD4 and CD8 development, and thymus cells tumorogenesis.
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spelling pubmed-49041182016-06-16 Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models Belizário, José E. Brandão, Wesley Rossato, Cristiano Peron, Jean Pierre Mediators Inflamm Review Article Our understanding of how thymocytes differentiate into many subtypes has been increased progressively in its complexity. At early life, the thymus provides a suitable microenvironment with specific combination of stromal cells, growth factors, cytokines, and chemokines to induce the bone marrow lymphoid progenitor T-cell precursors into single-positive CD4(+) and CD8(+) T effectors and CD4(+)CD25(+) T-regulatory cells (Tregs). At postthymic compartments, the CD4(+) T-cells acquire distinct phenotypes which include the classical T-helper 1 (Th1), T-helper 2 (Th2), T-helper 9 (Th9), T-helper 17 (Th17), follicular helper T-cell (Tfh), and induced T-regulatory cells (iTregs), such as the regulatory type 1 cells (Tr1) and transforming growth factor-β- (TGF-β-) producing CD4(+) T-cells (Th3). Tregs represent only a small fraction, 5–10% in mice and 1-2% in humans, of the overall CD4(+) T-cells in lymphoid tissues but are essential for immunoregulatory circuits mediating the inhibition and expansion of all lineages of T-cells. In this paper, we first provide an overview of the major cell-intrinsic developmental programs that regulate T-cell lineage fates in thymus and periphery. Next, we introduce the SV40 immortomouse as a relevant mice model for implementation of new approaches to investigate thymus organogenesis, CD4 and CD8 development, and thymus cells tumorogenesis. Hindawi Publishing Corporation 2016 2016-05-30 /pmc/articles/PMC4904118/ /pubmed/27313405 http://dx.doi.org/10.1155/2016/9523628 Text en Copyright © 2016 José E. Belizário et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Belizário, José E.
Brandão, Wesley
Rossato, Cristiano
Peron, Jean Pierre
Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title_full Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title_fullStr Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title_full_unstemmed Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title_short Thymic and Postthymic Regulation of Naïve CD4(+) T-Cell Lineage Fates in Humans and Mice Models
title_sort thymic and postthymic regulation of naïve cd4(+) t-cell lineage fates in humans and mice models
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904118/
https://www.ncbi.nlm.nih.gov/pubmed/27313405
http://dx.doi.org/10.1155/2016/9523628
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