γδ TCR repertoires remain stable during virus clearance by direct-acting anti-viral drug therapy.. Homo sapiens

Human γδ T cells are relatively frequent in the liver, comprising on average 15% of liver lymphocytes. They can contribute to viral clearance of hepatitis C (HCV) and mediate liver inflammation. This study aims at understanding the clonal distribution of γδ T cells during chronic HCV infection and during HCV clearance under novel antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next generation sequencing. While a few expanded Vδ3 clones could be identified in peripheral blood of 23 chronic HCV patients, overall clonality and complexity of γδ TCR repertoires were comparable to those of matched healthy donors. Monitoring eight chronic HCV patients before, during and up to one year after therapy revealed that direct-acting antiviral drug therapies do not alter TRG and TRD repertoires of Vγ9+ and Vγ9– cells. Together, we show that peripheral γδ TCR repertoires were undisturbed 1) by chronic HCV infection and 2) by HCV clearance in the course of direct-acting antiviral drug therapy.