Fate and Function of Hepatitis-C-Virus-Specific T-Cells during Peginterferon-α2b therapy for Acute Hepatitis C

Abstract

Background

Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8⁺ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity.

Methods

T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-α2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers.

Results

HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4⁺ and CD8⁺ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8⁺ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8⁺ T-cells by week 12.

Conclusions

Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.