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

J Infect Dis. 2019 Apr 16;219(9):1430-1438. doi: 10.1093/infdis/jiy679.

Abstract

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.

Keywords: CD8+ T cells; CXCR3; chemokine receptor; hepatitis C; liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Chemokine CXCL10 / metabolism
  • Chemokines / metabolism*
  • Female
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / metabolism*
  • Humans
  • Leukocyte Common Antigens / metabolism
  • Liver / immunology
  • Liver / metabolism
  • Male
  • Middle Aged
  • Receptors, CCR2 / metabolism
  • Receptors, CCR5 / metabolism
  • Receptors, CCR7 / metabolism
  • Receptors, CXCR3 / metabolism
  • Receptors, CXCR6 / metabolism
  • Receptors, Chemokine / metabolism*

Substances

  • CCR2 protein, human
  • CCR5 protein, human
  • CCR7 protein, human
  • CXCL10 protein, human
  • CXCR3 protein, human
  • CXCR6 protein, human
  • Chemokine CXCL10
  • Chemokines
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, CCR7
  • Receptors, CXCR3
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Leukocyte Common Antigens