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Nat Commun. 2017 May 3;8:15050. doi: 10.1038/ncomms15050.

TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation.

Author information

1
Department of Medicine II, University Hospital Freiburg - Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, Freiburg 79106, Germany.
2
Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg 79104, Germany.
3
Faculty of Biology, University of Freiburg, Freiburg 79104, Germany.
4
Institute for Cell and Gene Therapy, University Hospital Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
5
Institute of Molecular Immunology and Experimental Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaningerstr. 22, München 81675, Germany.
6
Ludwig Center for Cancer Research, Department of Fundamental Oncology, University of Lausanne, 155, Ch. Des Boveresses, Epalinges 1066, Switzerland.
7
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University Munich, Freising, Weihenstephaner Berg 3, Freising 85354, Germany.

Abstract

Differentiation and fate of virus-specific CD8+ T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1+CD127+PD1+ 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 TCF1+CD127+PD1+ population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1hi HCV-specific CD8+ T cells. These results suggest the TCF1+CD127+PD1+ 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.

PMID:
28466857
PMCID:
PMC5418623
DOI:
10.1038/ncomms15050
[Indexed for MEDLINE]
Free PMC Article

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