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


OBJECTIVE
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.
Boisvert
Judie
J
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. judie1@itsa.ucsf.edu
Kunkel
Eric J
EJ
Campbell
James J
JJ
Keeffe
Emmet B
EB
Butcher
Eugene C
EC
Greenberg
Harry B
HB
D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D006526:Hepatitis C / Q000473:pathology*; D006801:Humans; D007156:Immunologic Memory; D008099:Liver / Q000473:pathology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology* / Q000502:physiology; D010641:Phenotype; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism
D015415:Biomarkers; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing