Human γδ T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy

TY - JOUR

T1 - Human γδ T Cell Receptor Repertoires in Peripheral Blood Remain Stable Despite Clearance of Persistent Hepatitis C Virus Infection by Direct-Acting Antiviral Drug Therapy

AU - Ravens, Sarina

AU - Hengst, Julia

AU - Schlapphoff, Verena

AU - Deterding, Katja

AU - Dhingra, Akshay

AU - Schultze-Florey, Christian

AU - Koenecke, Christian

AU - Cornberg, Markus

AU - Wedemeyer, Heiner

AU - Prinz, Immo

PY - 2018/3/16

Y1 - 2018/3/16

N2 - Human γδ T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of γδ T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of Vγ9+ T cells was higher in patients with elevated liver enzymes and a few expanded Vδ3 clones could be identified in peripheral blood of 23 HCV-infected non-cirrhotic patients, overall clonality and complexity of γδ TCR repertoires were largely comparable to those of matched healthy donors. Monitoring eight chronic HCV patients before, during and up to 1 year after therapy revealed that direct-acting antiviral (DAA) drug therapies induced only minor alterations of TRG and TRD repertoires of Vγ9+ and Vγ9- cells. Together, we show that peripheral γδ TCR repertoires display a high stability (1) by chronic HCV infection in the absence of liver cirrhosis and (2) by HCV clearance in the course of DAA drug therapy.

AB - Human γδ T cells can contribute to clearance of hepatitis C virus (HCV) infection but also mediate liver inflammation. This study aimed to understand the clonal distribution of γδ T cells in peripheral blood of chronic HCV patients and following HCV clearance by interferon-free direct-acting antiviral drug therapies. To this end, γδ T cell receptor (TCR) repertoires were monitored by mRNA-based next-generation sequencing. While the percentage of Vγ9+ T cells was higher in patients with elevated liver enzymes and a few expanded Vδ3 clones could be identified in peripheral blood of 23 HCV-infected non-cirrhotic patients, overall clonality and complexity of γδ TCR repertoires were largely comparable to those of matched healthy donors. Monitoring eight chronic HCV patients before, during and up to 1 year after therapy revealed that direct-acting antiviral (DAA) drug therapies induced only minor alterations of TRG and TRD repertoires of Vγ9+ and Vγ9- cells. Together, we show that peripheral γδ TCR repertoires display a high stability (1) by chronic HCV infection in the absence of liver cirrhosis and (2) by HCV clearance in the course of DAA drug therapy.

KW - Adult

KW - Aged

KW - Antiviral Agents/therapeutic use

KW - Female

KW - Hepatitis C, Chronic/drug therapy

KW - Humans

KW - Intraepithelial Lymphocytes/immunology

KW - Lymphocyte Count

KW - Male

KW - Middle Aged

KW - Receptors, Antigen, T-Cell, gamma-delta/immunology

KW - Young Adult

U2 - 10.3389/fimmu.2018.00510

DO - 10.3389/fimmu.2018.00510

M3 - SCORING: Journal article

C2 - 29616028

VL - 9

SP - 510

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

ER -