Dynamic Changes in Ex Vivo T-Cell Function After Viral Clearance in Chronic HCV Infection
Ji Won Han1, Pil Soo Sung1,2,3, Kyung Hwan Kim1
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Background:
Direct-acting antiviral (DAA) agents can successfully treat chronic hepatitis C virus (HCV) infection. However, the ex vivo HCV-specific T-cell function following viral clearance remains unknown.
Methods:
We investigated functional alterations and phenotypic changes in ex vivo HCV-specific CD8+ T cells with a longitudinal analysis of 41 patients with chronic HCV infection who were undergoing DAA treatment.
Results:
A patient subset exhibited a significantly increased T-cell response (mainly CD8+ T cells) at week 4 of treatment. However, this increased T-cell response diminished in later weeks. Relative to pretreatment levels, the ex vivo HCV-specific CD8+ T-cell frequency decreased at 12 weeks after the end of treatment, along with a decreased antigen-experienced CD8+ T-cell population. DAA treatment increased the proliferative capacity of HCV-specific CD8+ T cells, but this change was not correlated with ex vivo function. Patients experiencing viral breakthrough or relapse exhibited defective restoration of T-cell function.
Conclusion:
Our present results indicated that DAA-mediated viral clearance only transiently restored ex vivo T-cell function, suggesting a need to enhance T-cell function in DAA-treated patients.
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