TCF1 Hepatitis C Virus-specific CD8 T Cells Are Maintained After Cessation of Chronic Antigen Stimulation

Overview

Journal Nat Commun

Specialty Biology

Date 2017 May 4

PMID 28466857

Citations 119

Authors

Dominik Wieland

Janine Kemming

Anita Schuch

Florian Emmerich

Percy Knolle

Christoph Neumann-Haefelin

Werner Held

Dietmar Zehn

Maike Hofmann

Robert Thimme

Affiliations

Soon will be listed here.

Abstract

Differentiation and fate of virus-specific CD8 T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1CD127PD1 hepatitis C virus (HCV)-specific CD8 T-cell subset exists in chronically infected patients with phenotypic features of T-cell exhaustion and memory, both before and after treatment with direct acting antiviral (DAA) agents. This subset is maintained during, and for a long duration after, HCV elimination. After antigen re-challenge the less differentiated TCF1CD127PD1 population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1 HCV-specific CD8 T cells. These results suggest the TCF1CD127PD1 HCV-specific CD8 T-cell subset has memory-like characteristics, including antigen-independent survival and recall proliferation. We thus provide evidence for the establishment of memory-like virus-specific CD8 T cells in a clinically relevant setting of chronic viral infection and we uncover their fate after cessation of chronic antigen stimulation, implicating a potential strategy for antiviral immunotherapy.

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