Chemokine-Regulated Recruitment Of Antigen-Specific T-Cell Subpopulations To The Liver In Acute And Chronic Hepatitis C Infection

Background. In hepatitis C virus (HCV) infection, virus-specific CD8(+) T cells are recruited to the liver for antiviral activity. Multiple chemokine ligands are induced by the infection, notably interferon-inducible chemokine, CXCL10. In HCV, intrahepatic T cells express chemokine receptors (CCRs), including CXCR3, CXCR6, CCR1, and CCR5, but CCR expression on antigen-specific effector and memory T cells has not been investigated.Methods. Paired blood and liver samples were collected from subjects with chronic HCV for flow cytometric analysis of CCR expression on CD8(+) T cells. Expression of these CCRs was then examined on HCV-specific CD8(+) T-cell subpopulations in the blood from subjects with acute or chronic HCV.Results. Relative to peripheral blood, the liver was enriched with CD8(+) T cells expressing CCR2, CCR5, CXCR3, and CXCR6 either singly or in combinations. CXCR3 was preferentially expressed on HCV-specific CD8+ T cells in both acute and chronic phases of infection in blood. Both CXCR3 and CCR2 were overexpressed on HCV-specific CD8(+)CCR7(+)CD45RO(+) (central memory) cells, whereas effector memory (CD8+ CCR7-CD45RO(+)) cells expressed more CXCR6.Conclusions. CXCR3-mediated signals support the accumulation of HCV-specific CD8(+) memory T cells in the infected liver, and emphasize the importance of the CXCL10/CXCR3 trafficking pathway during acute and chronic HCV infection.