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


CONCLUSIONS
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.).
Ye
Li
L
Department of Pediatrics, Division of Allergy and Immunology, Joseph Stokes, Jr Research Institute at The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wang
Xu
X
Wang
Shihong
S
Wang
Yanjian
Y
Song
Li
L
Hou
Wei
W
Zhou
Lin
L
Li
He
H
Ho
Wenzhe
W
D019002:CD56 Antigen / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000473:pathology / Q000517:prevention & control; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology*
D019002:CD56 Antigen; D016898:Interferon-alpha; D012367:RNA, Viral; D050791:STAT Transcription Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D053612:Janus Kinases