Apoptotic Epitope-Specific CD8+ T Cells and Interferon Signaling Intersect in Chronic Hepatitis C Virus Infection

J Infect Dis. 2016 Feb 15;213(4):674-83. doi: 10.1093/infdis/jiv460. Epub 2015 Sep 19.


CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper 1-like signature program in chronic HCV infection. However, apoptotic epitope-specific CD8(+) T cells produced tumor necrosis factor α and interleukin 2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations expressing high levels of programmed death 1 receptor. Contextually, only apoptotic epitope-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Together, these data suggest that, compared with HCV-specific CD8(+) T cells, apoptotic epitope-specific CD8(+) T cells can better sustain chronic immune activation, owing to their capacity to produce tumor necrosis factor α, and exhibit greater resistance to inhibitory signals during chronic HCV infection.

Keywords: CD8+ T cells; apoptosis; chronic immune activation; hepatitis C virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / pathology*
  • Humans
  • Interferons / metabolism*
  • Interleukin-2 / metabolism
  • Liver Cirrhosis / pathology
  • Male
  • Middle Aged
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferons