Imperial College London
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DrMargaritaDominguez-Villar

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3735m.dominguez-villar Website

 
 
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Location

 

117Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fernandez-Ponce:2014:10.1371/journal.pone.0085191,
author = {Fernandez-Ponce, C and Dominguez-Villar, M and Aguado, E and Garcia-Cozar, F},
doi = {10.1371/journal.pone.0085191},
journal = {PLoS ONE},
title = {CD4+primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells},
url = {http://dx.doi.org/10.1371/journal.pone.0085191},
volume = {9},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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+CD127lowPD-1highTIM-3high 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.
AU  - Fernandez-Ponce,C
AU  - Dominguez-Villar,M
AU  - Aguado,E
AU  - Garcia-Cozar,F
DO  - 10.1371/journal.pone.0085191
PY  - 2014///
SN  - 1932-6203
TI  - CD4+primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells
T2  - PLoS ONE
UR  - http://dx.doi.org/10.1371/journal.pone.0085191
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000330240500037&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/64011
VL  - 9
ER  -
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