Decrease of T-cells exhaustion markers programmed cell death-1 and T-cell immunoglobulin and mucin domain-containing protein 3 and plasma IL-10 levels after successful treatment of chronic hepatitis C

During chronic hepatitis C virus (HCV) infection, both CD4(+) and CD8(+) T-cells become functionally exhausted, which is reflected by increased expression of programmed cell death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and elevated anti-inflammatory interleukin 10 (IL-10) plasma levels. We studied 76 DAA-treated HCV-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4(+)PD-1(+), CD4(+)PD-1(+)Tim-3(+) and CD8(+)PD-1(+)Tim-3(+) T-cells and IL-10 levels measured by ELISA were significantly higher and CD4(+)PD-1(-)Tim-3(-) and CD8(+)PD-1(-)Tim-3(-) T-cells were significantly lower in patients than in controls. Treatment resulted in significant decrease of CD4(+)Tim-3(+), CD8(+)Tim-3(+), CD4(+)PD-1(+)Tim-3(+) and CD8(+)PD-1(+)Tim-3(+) T-cell frequencies as well as IL-10 levels and increase in CD4(+)PD-1(-)Tim-3(-) and CD8(+)PD-1(-)Tim-3(-) T-cells. There were no significant changes in the frequencies of CD4(+)PD-1(+) T-cells, while CD8(+)PD-1(+) T-cells increased. Patients with advanced liver fibrosis had higher PD-1 and lower Tim-3 expression on CD4(+)T-cells and treatment had little or no effect on the exhaustion markers. HCV-specific CD8(+)T-cells frequency has declined significantly after treatment, but their PD-1 and Tim-3 expression did not change. Successful treatment of chronic hepatitis C with DAA is associated with reversal of immune exhaustion phenotype, but this effect is absent in patients with advanced liver fibrosis.