Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals

<p>Abstract</p> <p>Background</p> <p>Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerate...

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Main Authors: Hirsch Geri, Bowmer M Ian, Howley Constance, Gallant Maureen, Barrett Lisa, Peltekian Kevork, Grant Michael
Format: Article
Language:English
Published: BMC 2008-06-01
Series:BMC Immunology
Online Access:http://www.biomedcentral.com/1471-2172/9/28
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spelling doaj-e0054ef1936f474c9de4830ee82c15fb2020-11-25T03:48:50ZengBMCBMC Immunology1471-21722008-06-01912810.1186/1471-2172-9-28Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individualsHirsch GeriBowmer M IanHowley ConstanceGallant MaureenBarrett LisaPeltekian KevorkGrant Michael<p>Abstract</p> <p>Background</p> <p>Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals.</p> <p>Results</p> <p>Intracellular flow cytometry was used to assess IL-2, IL-10, IL-12, and IFN-γ production by freshly isolated PBMC incubated for 16 hours with recombinant HCV core, non-structural protein 3 (NS3), and NS4 proteins. Anti-HCV cellular responses were assessed in HIV/HCV-coinfected individuals by <sup>3</sup>H-thymidine proliferation assay. Exposure to HCV antigens increased IL-10 production by PBMC, especially in uninfected and HIV-monoinfected individuals. This IL-10 response was attenuated in chronic HCV infection even with HCV/HIV-coinfection. The cells producing IL-10 in response to HCV proteins in vitro matched a PBMC subset recently shown to constitutively produce IL-10 in vivo. This subset was found at similar frequencies in uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals before exposure to HCV proteins. HCV-specific T cell proliferation was detectable in only one HIV/HCV-coinfected individual who demonstrated no HCV-induced IL-10 response.</p> <p>Conclusion</p> <p>This pattern suggests that selective induction of IL-10 in uninfected individuals and especially in HIV-monoinfected individuals plays a role in establishing chronic HCV infection and conversely, that attenuation of this response, once chronic infection is established, favours development of hepatic immunopathology.</p> http://www.biomedcentral.com/1471-2172/9/28
collection DOAJ
language English
format Article
sources DOAJ
author Hirsch Geri
Bowmer M Ian
Howley Constance
Gallant Maureen
Barrett Lisa
Peltekian Kevork
Grant Michael
spellingShingle Hirsch Geri
Bowmer M Ian
Howley Constance
Gallant Maureen
Barrett Lisa
Peltekian Kevork
Grant Michael
Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
BMC Immunology
author_facet Hirsch Geri
Bowmer M Ian
Howley Constance
Gallant Maureen
Barrett Lisa
Peltekian Kevork
Grant Michael
author_sort Hirsch Geri
title Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
title_short Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
title_full Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
title_fullStr Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
title_full_unstemmed Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
title_sort enhanced il-10 production in response to hepatitis c virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals
publisher BMC
series BMC Immunology
issn 1471-2172
publishDate 2008-06-01
description <p>Abstract</p> <p>Background</p> <p>Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals.</p> <p>Results</p> <p>Intracellular flow cytometry was used to assess IL-2, IL-10, IL-12, and IFN-γ production by freshly isolated PBMC incubated for 16 hours with recombinant HCV core, non-structural protein 3 (NS3), and NS4 proteins. Anti-HCV cellular responses were assessed in HIV/HCV-coinfected individuals by <sup>3</sup>H-thymidine proliferation assay. Exposure to HCV antigens increased IL-10 production by PBMC, especially in uninfected and HIV-monoinfected individuals. This IL-10 response was attenuated in chronic HCV infection even with HCV/HIV-coinfection. The cells producing IL-10 in response to HCV proteins in vitro matched a PBMC subset recently shown to constitutively produce IL-10 in vivo. This subset was found at similar frequencies in uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals before exposure to HCV proteins. HCV-specific T cell proliferation was detectable in only one HIV/HCV-coinfected individual who demonstrated no HCV-induced IL-10 response.</p> <p>Conclusion</p> <p>This pattern suggests that selective induction of IL-10 in uninfected individuals and especially in HIV-monoinfected individuals plays a role in establishing chronic HCV infection and conversely, that attenuation of this response, once chronic infection is established, favours development of hepatic immunopathology.</p>
url http://www.biomedcentral.com/1471-2172/9/28
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