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.

Abstract

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.

• Authors: Sylwia Osuch, Tomasz Laskus, Hanna Berak, Karol Perlejewski, Karin J Metzner, Marcin Paciorek, Marek Radkowski, Kamila Caraballo Cortés
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 16060 (09 29 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32994477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Biomarkers, Pharmacological
• CD3 Complex
• HAVCR2 protein, human
• Hepatitis A Virus Cellular Receptor 2
• IL10 protein, human
• Mucin-3
• Programmed Cell Death 1 Receptor
• Interleukin-10

Topics

• Adult
• Antiviral Agents (metabolism)
• Apoptosis
• Biomarkers, Pharmacological (blood)
• CD3 Complex (metabolism)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Flow Cytometry
• Hepatitis A Virus Cellular Receptor 2 (immunology)
• Hepatitis C, Chronic (metabolism, pathology, therapy)
• Humans
• Interleukin-10 (metabolism)
• Liver Cirrhosis (pathology)
• Male
• Middle Aged
• Mucin-3 (metabolism)
• Plasma (metabolism)
• Programmed Cell Death 1 Receptor (metabolism)