Cargando…

CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells

Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumul...

Descripción completa

Detalles Bibliográficos
Autores principales: Fernandez-Ponce, Cecilia, Dominguez-Villar, Margarita, Aguado, Enrique, Garcia-Cozar, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896374/
https://www.ncbi.nlm.nih.gov/pubmed/24465502
http://dx.doi.org/10.1371/journal.pone.0085191
_version_ 1782300070751764480
author Fernandez-Ponce, Cecilia
Dominguez-Villar, Margarita
Aguado, Enrique
Garcia-Cozar, Francisco
author_facet Fernandez-Ponce, Cecilia
Dominguez-Villar, Margarita
Aguado, Enrique
Garcia-Cozar, Francisco
author_sort Fernandez-Ponce, Cecilia
collection PubMed
description Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127(low)PD-1(high)TIM-3(high) regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein.
format Online
Article
Text
id pubmed-3896374
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38963742014-01-24 CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells Fernandez-Ponce, Cecilia Dominguez-Villar, Margarita Aguado, Enrique Garcia-Cozar, Francisco PLoS One Research Article Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127(low)PD-1(high)TIM-3(high) regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein. Public Library of Science 2014-01-20 /pmc/articles/PMC3896374/ /pubmed/24465502 http://dx.doi.org/10.1371/journal.pone.0085191 Text en © 2014 Fernandez-Ponce et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fernandez-Ponce, Cecilia
Dominguez-Villar, Margarita
Aguado, Enrique
Garcia-Cozar, Francisco
CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title_full CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title_fullStr CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title_full_unstemmed CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title_short CD4+ Primary T Cells Expressing HCV-Core Protein Upregulate Foxp3 and IL-10, Suppressing CD4 and CD8 T Cells
title_sort cd4+ primary t cells expressing hcv-core protein upregulate foxp3 and il-10, suppressing cd4 and cd8 t cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896374/
https://www.ncbi.nlm.nih.gov/pubmed/24465502
http://dx.doi.org/10.1371/journal.pone.0085191
work_keys_str_mv AT fernandezponcececilia cd4primarytcellsexpressinghcvcoreproteinupregulatefoxp3andil10suppressingcd4andcd8tcells
AT dominguezvillarmargarita cd4primarytcellsexpressinghcvcoreproteinupregulatefoxp3andil10suppressingcd4andcd8tcells
AT aguadoenrique cd4primarytcellsexpressinghcvcoreproteinupregulatefoxp3andil10suppressingcd4andcd8tcells
AT garciacozarfrancisco cd4primarytcellsexpressinghcvcoreproteinupregulatefoxp3andil10suppressingcd4andcd8tcells