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

Dominik Wieland, Janine Kemming, Anita Schuch, Florian Emmerich, Percy Knolle, Christoph Neumann-Haefelin, Werner Held, Dietmar Zehn, Maike Hofmann and Robert Thimme ()
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Dominik Wieland: University Hospital Freiburg — Faculty of Medicine, University of Freiburg
Janine Kemming: University Hospital Freiburg — Faculty of Medicine, University of Freiburg
Anita Schuch: University Hospital Freiburg — Faculty of Medicine, University of Freiburg
Florian Emmerich: Institute for Cell and Gene Therapy, University Hospital Freiburg
Percy Knolle: Institute of Molecular Immunology and Experimental Oncology, Technische Universität München
Christoph Neumann-Haefelin: University Hospital Freiburg — Faculty of Medicine, University of Freiburg
Werner Held: Ludwig Center for Cancer Research, University of Lausanne
Dietmar Zehn: School of Life Sciences Weihenstephan, Technical University Munich
Maike Hofmann: University Hospital Freiburg — Faculty of Medicine, University of Freiburg
Robert Thimme: University Hospital Freiburg — Faculty of Medicine, University of Freiburg

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15050

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