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A more recent version of this article appeared on October 1, 2004

Published online before print June 24, 2004
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0304197


Received for publication March 25, 2004.

Accepted for publication May 24, 2004.


Article

Role of NK and NKT cells in the immunopathogenesis of HCV-induced hepatitis

Ali Ahmad *{ddagger}@ and Fernando Alvarez {dagger}{ddagger}

Departments of *Microbiology & Immunology and {dagger}Pediatrics and {ddagger}Center of Research, Ste. Justine Hospital, University of Montreal, Quebec, Canada

@ To whom correspondence should be addressed. E-mail: ahmada{at}justine.umontreal.ca.


   Abstract

Natural killer (NK) cells constitute the first line of host defense against invading pathogens. They usually become activated in an early phase of a viral infection. Liver is particularly enriched in NK cells, which are activated by hepatotropic viruses such as hepatitis C virus (HCV). The activated NK cells play an essential role in recruiting virus-specific T cells and in inducing antiviral immunity in liver. They also eliminate virus-infected hepatocytes directly by cytolytic mechanisms and indirectly by secreting cytokines, which induce an antiviral state in host cells. Therefore, optimally activated NK cells are important in limiting viral replication in this organ. This notion is supported by the observations that interferon treatment is effective in HCV-infected persons in whom it increases NK cell activity. Thus, it is not surprising that HCV has evolved multiple strategies to counter host’s NK cell response. Compromised NK cell functions have been reported in chronic HCV-infected individuals. It is ironic that activated NK cells may also contribute toward liver injury. Further studies are needed to understand the role of these cells in host defense and in liver pathology in HCV infections. Recent advances in understanding NK cell biology have opened new avenues for boosting innate and adaptive antiviral immune responses in HCV-infected individuals.




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