HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection

PLoS One. 2016 Apr 28;11(4):e0154433. doi: 10.1371/journal.pone.0154433. eCollection 2016.

Abstract

Background: Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.

Methods: We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.

Results: In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.

Conclusions: These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / virology
  • Coinfection
  • Cross-Sectional Studies
  • Female
  • Gene Expression
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / growth & development
  • HIV-1 / immunology
  • Hepacivirus / growth & development
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunity, Cellular*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Viral Load / immunology

Substances

  • IL17A protein, human
  • Interleukin-17
  • Interleukins
  • interleukin-21

Grants and funding

Research conducted by the authors is supported by Canfar grant #021–012 to M.A.O. S.A.M. thanks the CASL/CIHR Hepatology Fellowship Program and the National CIHR Research Training Program in Hepatitis C for financial support. S.M.F. and A.F. thank the National CIHR Research Training Program in Hepatitis C for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.