Frontiers in Immunology (Dec 2022)
Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling
- Felix Schreibing,
- Felix Schreibing,
- Monica T. Hannani,
- Monica T. Hannani,
- Hyojin Kim,
- James S. Nagai,
- James S. Nagai,
- Fabio Ticconi,
- Fabio Ticconi,
- Eleanor Fewings,
- Tore Bleckwehl,
- Matthias Begemann,
- Natalia Torow,
- Christoph Kuppe,
- Christoph Kuppe,
- Ingo Kurth,
- Jennifer Kranz,
- Jennifer Kranz,
- Jennifer Kranz,
- Dario Frank,
- Teresa M. Anslinger,
- Teresa M. Anslinger,
- Patrick Ziegler,
- Thomas Kraus,
- Jürgen Enczmann,
- Vera Balz,
- Frank Windhofer,
- Paul Balfanz,
- Christian Kurts,
- Gernot Marx,
- Nikolaus Marx,
- Michael Dreher,
- Rebekka K. Schneider,
- Rebekka K. Schneider,
- Julio Saez-Rodriguez,
- Julio Saez-Rodriguez,
- Ivan Costa,
- Ivan Costa,
- Sikander Hayat,
- Rafael Kramann,
- Rafael Kramann,
- Rafael Kramann
Affiliations
- Felix Schreibing
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Felix Schreibing
- Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany
- Monica T. Hannani
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Monica T. Hannani
- Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany
- Hyojin Kim
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- James S. Nagai
- Institute for Computational Genomics, Medical Faculty, RWTH Aachen University, Aachen, Germany
- James S. Nagai
- Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
- Fabio Ticconi
- Institute for Computational Genomics, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Fabio Ticconi
- Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
- Eleanor Fewings
- Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany
- Tore Bleckwehl
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Matthias Begemann
- Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Natalia Torow
- Institute of Medical Microbiology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Christoph Kuppe
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Christoph Kuppe
- Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany
- Ingo Kurth
- Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Jennifer Kranz
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Jennifer Kranz
- Department of Urology and Pediatric Urology, RWTH Aachen University, Aachen, Germany
- Jennifer Kranz
- Department of Urology and Kidney Transplantation, Martin Luther University (Saale), Halle, Germany
- Dario Frank
- 0Department of Medicine, St Antonius Hospital, Eschweiler, Germany
- Teresa M. Anslinger
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Teresa M. Anslinger
- Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany
- Patrick Ziegler
- 1Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Thomas Kraus
- 1Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Jürgen Enczmann
- 2Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany
- Vera Balz
- 2Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany
- Frank Windhofer
- 2Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany
- Paul Balfanz
- 3Department of Cardiology, Angiology and Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Christian Kurts
- 4Institute of Molecular Medicine and Experimental Immunology, Medical Faculty, University of Bonn, Bonn, Germany
- Gernot Marx
- 5Department of Intensive and Intermediate Care, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Nikolaus Marx
- 3Department of Cardiology, Angiology and Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Michael Dreher
- 6Department of Pneumology and Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Rebekka K. Schneider
- 7Institute of Cell and Tumor Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Rebekka K. Schneider
- 8Department of Developmental Biology, Erasmus Medical Center, Rotterdam, Netherlands
- Julio Saez-Rodriguez
- Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany
- Julio Saez-Rodriguez
- Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
- Ivan Costa
- Institute for Computational Genomics, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Ivan Costa
- Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
- Sikander Hayat
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Rafael Kramann
- Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany
- Rafael Kramann
- Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany
- Rafael Kramann
- 9Department of Internal Medicine, Erasmus Medical Center (MC), Rotterdam, Netherlands
- DOI
- https://doi.org/10.3389/fimmu.2022.1066176
- Journal volume & issue
-
Vol. 13
Abstract
IntroductionSARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants.MethodsWe combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19.ResultsWe observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions.DiscussionWe propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.
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