Document Detail


Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor beta that can suppress HCV-specific T-cell responses.
MedLine Citation:
PMID:  17376924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatitis C virus (HCV)-specific T-cell responses are rarely detected in peripheral blood, especially in the presence of human immunodeficiency virus (HIV) coinfection. Based on recent evidence that T-regulatory cells may be increased in chronic HCV, we hypothesized that functional blockade of regulatory cells could raise HCV-specific responses and might be differentially regulated in the setting of HIV coinfection. Three groups of subjects were studied: HCV monoinfected, HCV-HIV coinfected, and healthy controls. Frequencies of peripheral T cells specific for peptides derived from HCV core, HIV type 1 p24, and recall antigens were analyzed by gamma interferon (IFN-gamma) enzyme-linked immuno-spot assay. HCV-specific T-cell responses were very weak in groups with HCV and HCV-HIV infections. Addition of blocking antibodies against transforming growth factor beta1 (TGF-beta1), -2, and -3 and interleukin-10 specifically increased the HCV-specific T-cell responses in both infected groups; however, this increase was attenuated in the group with HCV-HIV coinfection compared to HCV infection alone. No increase in recall antigen- or HIV-specific responses was observed. Flow cytometric sorter analysis demonstrated that regulatory-associated cytokines were produced by HCV-specific CD3(+)CD8(+)CD25(-) cells. Enhancement of the IFN-gamma effect was observed for both CD4 and CD8 T cells and was mediated primarily by TGF-beta1, -2, and -3 neutralization. In conclusion, blockade of TGF-beta secretion could enhance peripheral HCV-specific T-cell responses even in the presence of HIV coinfection.
Authors:
Nadia Alatrakchi; Camilla S Graham; Hans J J van der Vliet; Kenneth E Sherman; Mark A Exley; Margaret James Koziel
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-21
Journal Detail:
Title:  Journal of virology     Volume:  81     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-14     Completed Date:  2007-07-12     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5882-92     Citation Subset:  IM    
Affiliation:
Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA. nalatrak@bidmc.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
CD8-Positive T-Lymphocytes / immunology*,  metabolism,  virology*
Cells, Cultured
Chronic Disease
Female
HIV-1 / immunology
Hepacivirus / immunology*
Humans
Interferon-gamma / antagonists & inhibitors,  biosynthesis
Male
Middle Aged
Transforming Growth Factor beta / biosynthesis*,  physiology
Grant Support
ID/Acronym/Agency:
AI49508/AI/NIAID NIH HHS; DA14495-01/DA/NIDA NIH HHS; DK066917/DK/NIDDK NIH HHS; P30 A060354//PHS HHS; P30 AI060354/AI/NIAID NIH HHS; U19 AI066313/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; 82115-62-6/Interferon-gamma
Comments/Corrections

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