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Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3

CD4(+)CD25(+) regulatory T cells (T(reg)) are instrumental in the maintenance of immunological tolerance. One critical question is whether T(reg) can only be generated in the thymus or can differentiate from peripheral CD4(+)CD25(−) naive T cells. In this paper, we present novel evidence that conver...

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Autores principales: Chen, WanJun, Jin, Wenwen, Hardegen, Neil, Lei, Ke-jian, Li, Li, Marinos, Nancy, McGrady, George, Wahl, Sharon M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194145/
https://www.ncbi.nlm.nih.gov/pubmed/14676299
http://dx.doi.org/10.1084/jem.20030152
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author Chen, WanJun
Jin, Wenwen
Hardegen, Neil
Lei, Ke-jian
Li, Li
Marinos, Nancy
McGrady, George
Wahl, Sharon M.
author_facet Chen, WanJun
Jin, Wenwen
Hardegen, Neil
Lei, Ke-jian
Li, Li
Marinos, Nancy
McGrady, George
Wahl, Sharon M.
author_sort Chen, WanJun
collection PubMed
description CD4(+)CD25(+) regulatory T cells (T(reg)) are instrumental in the maintenance of immunological tolerance. One critical question is whether T(reg) can only be generated in the thymus or can differentiate from peripheral CD4(+)CD25(−) naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4(+)CD25(−) T cells into anergic/suppressor cells that are CD25(+), CD45RB(−/low) and intracellular CTLA-4(+) can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β). Although transcription factor Foxp3 has been shown recently to be associated with the development of T(reg), the physiological inducers for Foxp3 gene expression remain a mystery. TGF-β induced Foxp3 gene expression in TCR-challenged CD4(+)CD25(−) naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-β and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-β–converted transgenic CD4(+)CD25(+) suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4(+) T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-β–induced suppressor T cells prevented house dust mite–induced allergic pathogenesis in lungs.
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spelling pubmed-21941452008-04-11 Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3 Chen, WanJun Jin, Wenwen Hardegen, Neil Lei, Ke-jian Li, Li Marinos, Nancy McGrady, George Wahl, Sharon M. J Exp Med Article CD4(+)CD25(+) regulatory T cells (T(reg)) are instrumental in the maintenance of immunological tolerance. One critical question is whether T(reg) can only be generated in the thymus or can differentiate from peripheral CD4(+)CD25(−) naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4(+)CD25(−) T cells into anergic/suppressor cells that are CD25(+), CD45RB(−/low) and intracellular CTLA-4(+) can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β). Although transcription factor Foxp3 has been shown recently to be associated with the development of T(reg), the physiological inducers for Foxp3 gene expression remain a mystery. TGF-β induced Foxp3 gene expression in TCR-challenged CD4(+)CD25(−) naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-β and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-β–converted transgenic CD4(+)CD25(+) suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4(+) T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-β–induced suppressor T cells prevented house dust mite–induced allergic pathogenesis in lungs. The Rockefeller University Press 2003-12-15 /pmc/articles/PMC2194145/ /pubmed/14676299 http://dx.doi.org/10.1084/jem.20030152 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Chen, WanJun
Jin, Wenwen
Hardegen, Neil
Lei, Ke-jian
Li, Li
Marinos, Nancy
McGrady, George
Wahl, Sharon M.
Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title_full Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title_fullStr Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title_full_unstemmed Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title_short Conversion of Peripheral CD4(+)CD25(−) Naive T Cells to CD4(+)CD25(+) Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
title_sort conversion of peripheral cd4(+)cd25(−) naive t cells to cd4(+)cd25(+) regulatory t cells by tgf-β induction of transcription factor foxp3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194145/
https://www.ncbi.nlm.nih.gov/pubmed/14676299
http://dx.doi.org/10.1084/jem.20030152
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