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.