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Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.
Schreibing, Felix; Hannani, Monica T; Kim, Hyojin; Nagai, James S; Ticconi, Fabio; Fewings, Eleanor; Bleckwehl, Tore; Begemann, Matthias; Torow, Natalia; Kuppe, Christoph; Kurth, Ingo; Kranz, Jennifer; Frank, Dario; Anslinger, Teresa M; Ziegler, Patrick; Kraus, Thomas; Enczmann, Jürgen; Balz, Vera; Windhofer, Frank; Balfanz, Paul; Kurts, Christian; Marx, Gernot; Marx, Nikolaus; Dreher, Michael; Schneider, Rebekka K; Saez-Rodriguez, Julio; Costa, Ivan; Hayat, Sikander; Kramann, Rafael.
  • Schreibing F; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Hannani MT; Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Kim H; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Nagai JS; Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
  • Ticconi F; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Fewings E; Institute for Computational Genomics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Bleckwehl T; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany.
  • Begemann M; Institute for Computational Genomics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Torow N; Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany.
  • Kuppe C; Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
  • Kurth I; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Kranz J; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Frank D; Institute of Medical Microbiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Anslinger TM; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Ziegler P; Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Kraus T; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Enczmann J; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Balz V; Department of Urology and Pediatric Urology, RWTH Aachen University, Aachen, Germany.
  • Windhofer F; Department of Urology and Kidney Transplantation, Martin Luther University (Saale), Halle, Germany.
  • Balfanz P; Department of Medicine, St Antonius Hospital, Eschweiler, Germany.
  • Kurts C; Institute of Experimental Medicine and Systems Biology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Marx G; Department of Renal and Hypertensive Disorders, Rheumatological and Immunological Diseases (Medical Clinic II), Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Marx N; Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Dreher M; Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Schneider RK; Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Saez-Rodriguez J; Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Costa I; Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, University Hospital Düsseldorf, Düsseldorf, Germany.
  • Hayat S; Department of Cardiology, Angiology and Intensive Care Medicine, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • Kramann R; Institute of Molecular Medicine and Experimental Immunology, Medical Faculty, University of Bonn, Bonn, Germany.
Front Immunol ; 13: 1066176, 2022.
Article in English | MEDLINE | ID: covidwho-2198907
ABSTRACT

Introduction:

SARS-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.

Methods:

We 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.

Results:

We 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.

Discussion:

We 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / COVID-19 Type of study: Prognostic study / Qualitative research Topics: Vaccines / Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.1066176

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Full text: Available Collection: International databases Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / COVID-19 Type of study: Prognostic study / Qualitative research Topics: Vaccines / Variants Limits: Humans Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.1066176