CD56+ T cells inhibit hepatitis C virus replication in human hepatocytes

Hepatology. 2009 Mar;49(3):753-62. doi: 10.1002/hep.22715.


CD56(+) T cells are abundant in liver and play an important role in defense against viral infections. However, the role of CD56(+) T cells in control of hepatitis C virus (HCV) infection remains to be determined. We investigated the noncytolytic anti-HCV activity of primary CD56(+) T cells in human hepatocytes. When HCV Japanese fulminant hepatitis-1 (JFH-1)-infected hepatocytes were co-cultured with CD56(+) T cells or incubated in media conditioned with CD56(+) T cell culture supernatants (SN), HCV infectivity and replication were significantly inhibited. The antibodies to interferon (IFN)-gamma or IFN-gamma receptor could largely block CD56(+) T cell-mediated anti-HCV activity. Investigation of mechanism(s) responsible for CD56(+) T cell-mediated noncytolytic anti-HCV activity showed that CD56(+) T SN activated the multiple elements of janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and enhanced the expression of IFN regulatory factors (IRFs) 1, 3, 7, 8, and 9, resulting in the induction of endogenous IFN-alpha/beta expression in hepatocytes. Moreover, CD56(+) T SN treatment inhibited the expression of HCV-supportive micro RNA (miRNA)-122 and enhanced the levels of anti-HCV miRNA-196a in human hepatocytes.

Conclusion: These findings provide direct in vitro evidence at cellular and molecular levels that CD56(+) T cells may have an essential role in innate immune cell-mediated defense against HCV infection. (HEPATOLOGY 2009.).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD56 Antigen / metabolism*
  • Cell Communication / physiology
  • Cell Line
  • Cells, Cultured
  • Coculture Techniques
  • Female
  • Hepacivirus / genetics
  • Hepacivirus / physiology*
  • Hepatitis C / pathology
  • Hepatitis C / prevention & control
  • Hepatocytes / metabolism
  • Hepatocytes / pathology*
  • Hepatocytes / virology*
  • Humans
  • Interferon-alpha / metabolism
  • Interferon-beta / metabolism
  • Interferon-gamma / metabolism
  • Janus Kinases / metabolism
  • Male
  • RNA, Viral / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / physiology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Virus Replication / physiology*


  • CD56 Antigen
  • Interferon-alpha
  • RNA, Viral
  • STAT Transcription Factors
  • Interferon-beta
  • Interferon-gamma
  • Janus Kinases