Positioning of leukocyte subsets in the portal and lobular compartments of hepatitis C virus-infected liver correlates with local chemokine expression

Background and Aim: Chronic hepatitis C virus infection is characterized by infiltration of a mixed population of leukocytes into portal tracts and infiltration almost exclusively by CD8+ T cells into lobules of the liver. This pattern of leukocyte recruitment is likely to be orchestrated in a cell-specific fashion by local chemokine expression. Methods: Portal or lobular tissues were isolated by laser capture microdissection from 17 liver biopsy specimens to examine regional gene expression of a panel of chemokine ligands and receptors. The biopsies were also stained immunohistochemically to enumerate regional cell numbers. Results: Expression of multiple chemokine ligands and receptors was evident, although few correlated with leukocyte numbers. In the lobule, expression of CXCL10 correlated with T-cell subsets (CD3+, P=0.0002; CD4+, P=0.0053; and CD8+, P=0.0061), as did CCL5 (CD3+, P=0.0005; CD8+, P=0.0199) and CCL3 (CD3+, P=0.0016; CD8+, P=0.008). In the portal tracts, expression of CXCL10 and CCL5 was correlated with CD8+ T-cell numbers (P=0.0040 and P=0.0114, respectively), whereas CXCL13 was strongly correlated with CD20+ B-cell numbers (P<0.0001). CXCR3 expression correlated with CD3+ and CD4+ T cells (P<0.0001 and P=0.0208, respectively), CCR5 with CD8+ T cells (P<0.0001), and CXCR5 with CD20+ B-cell infiltration (P=0.0022). Conclusion: CXCR3, CCR5, and CXCR5 and their ligands form key elements of the "zip code" responsible for regional localization of specific lymphocyte subsets in the HCV-infected liver.

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