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...

Full description

Saved in:
Bibliographic Details
Main Authors: José E. Belizário, Wesley Brandão, Cristiano Rossato, Jean Pierre Peron
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/9523628
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849682891678679040
author José E. Belizário
Wesley Brandão
Cristiano Rossato
Jean Pierre Peron
author_facet José E. Belizário
Wesley Brandão
Cristiano Rossato
Jean Pierre Peron
author_sort José E. Belizário
collection DOAJ
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.
format Article
id doaj-art-c97366dc4cb24072ae91cfdad78293ed
institution DOAJ
issn 0962-9351
1466-1861
language English
publishDate 2016-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-c97366dc4cb24072ae91cfdad78293ed2025-08-20T03:24:03ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/95236289523628Thymic and Postthymic Regulation of Naïve CD4+ T-Cell Lineage Fates in Humans and Mice ModelsJosé E. Belizário0Wesley Brandão1Cristiano Rossato2Jean Pierre Peron3Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, BrazilOur 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.http://dx.doi.org/10.1155/2016/9523628
spellingShingle José E. Belizário
Wesley Brandão
Cristiano Rossato
Jean Pierre Peron
Thymic and Postthymic Regulation of Naïve CD4+ T-Cell Lineage Fates in Humans and Mice Models
Mediators of Inflammation
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 naive cd4 t cell lineage fates in humans and mice models
url http://dx.doi.org/10.1155/2016/9523628
work_keys_str_mv AT joseebelizario thymicandpostthymicregulationofnaivecd4tcelllineagefatesinhumansandmicemodels
AT wesleybrandao thymicandpostthymicregulationofnaivecd4tcelllineagefatesinhumansandmicemodels
AT cristianorossato thymicandpostthymicregulationofnaivecd4tcelllineagefatesinhumansandmicemodels
AT jeanpierreperon thymicandpostthymicregulationofnaivecd4tcelllineagefatesinhumansandmicemodels