title: HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sonya A
authors.initials: SA
authors.lastname: MacParland
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Saleh M
authors.initials: SM
authors.lastname: Fadel
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vesna
authors.initials: V
authors.lastname: Mihajlovic
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Fawaz
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.|Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Connie
authors.initials: C
authors.lastname: Kim
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A K M Nur-Ur
authors.initials: AK
authors.lastname: Rahman
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.|Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
authors.affiliation: Maple Leaf Clinic, Toronto, Ontario, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: Kovacs
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Toronto General Hospital, Toronto, Ontario, Canada.
authors.forename: David K
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Departments of Immunology and Medicine, University of Toronto, Toronto, Ontario, Canada.|Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D060085:Coinfection; D003430:Cross-Sectional Studies; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D019562:Viral Load / Q000276:immunology; D000098546:Interleukin-21
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D007378:Interleukins; D000098546:Interleukin-21