Chemokine-Regulated Recruitment of Antigen-Specific T-Cell Subpopulations to the Liver in Acute and Chronic Hepatitis C Infection.

Abstract

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. 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. 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. 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.