Lymphocyte distribution and intrahepatic compartmentalization during HCV infection: A main role for MHC-unrestricted T cells

Chiara Agrati, Carla Nisii, Alessandra Oliva, Gianpiero D'Offizi, Carla Montesano, Leopoldo Paolo Pucillo, Fabrizio Poccia

Research output: Contribution to journalArticlepeer-review


Hepatitis C virus (HCV) infection induces an acute and chronic liver inflammation through an immune-mediated pathway that may lead to cirrhosis and liver failure. Indeed, HCV-related hepatitis is characterized by a dramatic lymphocyte infiltrate into the liver which is mainly composed by HCV non-specific cells. Several data indicated that interferon (IFN)-γ secretion by intrahepatic lymphocytes (IHL) may drive non-specific cell homing to the liver, inducing interferon inducible protein-10 (IP-10) production. An interesting hallmark of these IHL is the recruitment of lymphocytes associated with mechanisms of innate immunity, such as natural killer (NK), natural killer T (NKT) and γδ T lymphocytes. CD81 triggering on NK cell surface by the HCV envelope glycoprotein E2 was recently shown to inhibit NK cell function in the liver of HCV-infected persons, resulting in a possible mechanism contributing to the lack of virus clearance and to the establishment of chronic infection. In contrast, intrahepatic NKT cells restricted to CD1d molecules expressed on the hepatocyte surface may contribute to a large extent to liver damage. Finally, an increased frequency of T cells expressing the γδ T cell receptor (TCR) was observed in HCV-infected liver and recent observations indicate that intrahepatic γδ T cell activation could be directly induced by the HCV/E2 particle through CD81 triggering. These cells are not HCV specific, are able to kill target cells including primary hepatocytes and their ability to produce T helper (Th)1 cytokines is associated with a higher degree of liver disease. Together, CD1d/NKT and/or E2/CD81 interactions may play a major role in the establishment of HCV immunopathogenesis. In the absence of virus clearance, the chemokine-driven recruitment of lymphocytes with an innate cytotoxic behavior in the liver of HCV-infected patients may boost itself, leading to necroinflammatory and fibrotic liver disease.

Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalArchivum Immunologiae et Therapiae Experimentalis
Issue number5
Publication statusPublished - 2002


  • γδ T lymphocytes
  • CD1
  • CD81
  • E2
  • Hepatitis C
  • HLA
  • Intrahepatic lymphocytes
  • Liver
  • NK cells
  • NKT cells
  • NT cells

ASJC Scopus subject areas

  • Immunology


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