Liver-infiltrating lymphocytes in end-stage hepatitis C virus: subsets, activation status, and chemokine receptor phenotypes

J Hepatol. 2003 Jan;38(1):67-75. doi: 10.1016/s0168-8278(02)00328-8.

Abstract

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, yet little is known about the intrahepatic immune response in end-stage patients. Chemokines and their receptors are important regulators of immunity, particularly in the migration and localization of circulating leukocytes within peripheral tissues.

Aims: This report provides a comprehensive comparison of the chemokine receptor and activation phenotype of the major leukocyte subsets present in end-stage HCV-infected and non-HCV infected livers.

Methods: Lymphocytes were purified from homogenized explant liver tissue and analyzed by flow cytometry.

Results: NK cells are the predominant cell type, followed by T cells, B cells and NK-T cells, independent of HCV status. T cells displayed a memory phenotype and low levels of activation markers. CCR5, CXCR3 and CXCR6 were expressed on a large fraction of activated cells, while moderate to low expression of CCR2, CCR6 and CX(3)CR1 was observed. Several other tissue-specific and inflammatory chemokine receptors were absent from infiltrating lymphocytes.

Conclusions: These results identify the chemokine receptors present on infiltrating lymphocytes during end-stage liver disease and suggest that such infiltration is predominantly controlled by non-tissue-specific inflammatory chemokines, a situation that may be distinct from liver homing pathways under normal conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers / analysis
  • Case-Control Studies
  • Hepatitis C / pathology*
  • Humans
  • Immunologic Memory
  • Liver / pathology*
  • Lymphocyte Activation
  • Lymphocyte Subsets / pathology
  • Lymphocytes / pathology*
  • Lymphocytes / physiology
  • Phenotype
  • Receptors, Chemokine / genetics*
  • Receptors, Chemokine / metabolism*
  • Receptors, Lymphocyte Homing / metabolism

Substances

  • Biomarkers
  • Receptors, Chemokine
  • Receptors, Lymphocyte Homing