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

Author

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  • Dominik Wieland

    (University Hospital Freiburg — Faculty of Medicine, University of Freiburg
    Spemann Graduate School of Biology and Medicine, University of Freiburg
    Faculty of Biology, University of Freiburg)

  • Janine Kemming

    (University Hospital Freiburg — Faculty of Medicine, University of Freiburg
    Faculty of Biology, University of Freiburg)

  • Anita Schuch

    (University Hospital Freiburg — Faculty of Medicine, University of Freiburg
    Faculty of Biology, 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)

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.

Suggested Citation

  • Dominik Wieland & Janine Kemming & Anita Schuch & Florian Emmerich & Percy Knolle & Christoph Neumann-Haefelin & Werner Held & Dietmar Zehn & Maike Hofmann & Robert Thimme, 2017. "TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation," Nature Communications, Nature, vol. 8(1), pages 1-13, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15050
    DOI: 10.1038/ncomms15050
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    Cited by:

    1. Hideki Ogura & Jin Gohda & Xiuyuan Lu & Mizuki Yamamoto & Yoshio Takesue & Aoi Son & Sadayuki Doi & Kazuyuki Matsushita & Fumitaka Isobe & Yoshihiro Fukuda & Tai-Ping Huang & Takamasa Ueno & Naomi Mam, 2022. "Dysfunctional Sars-CoV-2-M protein-specific cytotoxic T lymphocytes in patients recovering from severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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