Research article

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

Lisa Barrett^1,4 , Maureen Gallant¹ , Constance Howley² , M Ian Bowmer² , Geri Hirsch³ , Kevork Peltekian^3,4 and Michael Grant¹

¹Immunology and Infectious Diseases Program, Division of BioMedical Sciences, Faculty of Medicine, Memorial University, St. John's, Canada

²HIV Program, Eastern Health District, St. John's, Canada

³Hepatitis C Program, Division of Gastroenterology, Capital Health District, Halifax, Canada

⁴Department of Internal Medicine, Dalhousie University, Halifax, Canada

author email corresponding author email

BMC Immunology 2008, 9:28doi:10.1186/1471-2172-9-28

Published:	13 June 2008

Abstract

Background

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.

Results

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 ³H-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.

Conclusion

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.