Upregulation of CXCR3 expression on CD8+ T cells due to the pervasive influence of chronic hepatitis B and C virus infection

Chronic systemic ‘latent’ viral infections such as Cytomegalovirus infection (CMV) are known to leave a fingerprint in the total T-cell population. We investigated whether chronic infections with a ‘persistent’ viremia, such as chronic hepatitis B and C (CHB, CHC), characterized by local organ-specific inflammation, also impact the total peripheral T-cell population or other virus specific T-cells that do not target hepatitis viruses.No phenotypic or functional differences were found between CD8+ T-cells or CMV- or Epstein–Barr virus specific T-cells in viral hepatitis and healthy controls (HC). However, expression of chemokine-receptor CXCR3 was significantly higher on total peripheral CD8+ T-cells of CHB or CHC patients compared to HC (p < 0.005) which may reflect the pervasive influence of a persistent viral infection, even when restricted to the liver. In CHB higher CXCR3 expression was associated with positive HBeAg-status and correlated with the percentage of HBsAg expressing hepatocytes found in liver biopsies, both pointing to a relation between CXCR3 expression and disease activity. In fact chemokine-receptors such as CXCR3 are important for T-cell recruitment to the liver and chemokine-ligands specific for CXCR3 are upregulated in chronic hepatitis. Modulating chemokine(receptor) expression could be a potential target for future therapy to optimize the anti-viral immunologic environment in the liver.