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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.

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


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.

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