CD3(+)CD56(+) Natural Killer-Like T Cells Display Anti-HCV Activity but Are Functionally Impaired in HIV(+) Patients With Acute Hepatitis C

J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):338-46. doi: 10.1097/QAI.0000000000000793.

Abstract

Objective: To analyze the role of CD3(+)CD56(+) natural killer (NK)-like T cells in HIV(+) patients with acute hepatitis C.

Design: Frequency, phenotype, and anti-hepatitis C virus (HCV) activity of CD3(+)CD56(+) NK-like T cells were studied in 36 HIV(+) patients with acute hepatitis C. As controls, 12 patients with chronic HCV/HIV coinfection, 8 HIV monoinfected patients, and 12 healthy donors were enrolled in this study.

Methods: CD3(+)CD56(+) NK-like T-cell-mediated inhibition of HCV replication was analyzed using the HuH7A2HCVreplicon model. The CD3(+)CD56(+) NK-like T-cell phenotype and interferon (IFN)-γ secretion were studied by flow cytometry.

Results: Interleukin 12/interleukin 15 stimulated CD3(+)CD56(+) NK-like T cells from healthy donors effectively block HCV replication in vitro in an IFN-γ dependent manner. Accordingly, we found that blocking of IFN-γ with a specific antibody significantly reduced the antiviral activity of CD3(+)CD56(+) NK-like T cells. However, when CD3(+)CD56(+) NK-like T cells from HIV(+) patients were studied, we found HIV infection to be associated with a significantly impaired IFN-γ production, irrespective of HCV coinfection. Accordingly, CD3(+)CD56(+) NK-like T cells from HIV(+) patients were significantly less effective in blocking HCV replication in vitro than cells from healthy individuals.

Conclusions: Taken together, our data indicate that HIV infection is associated with an impaired anti-HCV activity of CD3(+)CD56(+) NK-like T cells, which might represent a novel mechanism of dysregulated immune response in HIV/HCV-coinfected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD3 Complex / analysis*
  • CD56 Antigen / analysis*
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • HIV Infections / complications*
  • Hepacivirus / immunology*
  • Hepacivirus / physiology
  • Hepatitis C / immunology*
  • Hepatocytes / virology
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Natural Killer T-Cells / chemistry
  • Natural Killer T-Cells / immunology*
  • T-Lymphocyte Subsets / immunology
  • Virus Replication
  • Young Adult

Substances

  • CD3 Complex
  • CD56 Antigen
  • NCAM1 protein, human
  • Interferon-gamma