Journal Article

DZNE-2022-00698

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Complement activation induces excessive T cell cytotoxicity in severe COVID-19.

Georg, P. ; Astaburuaga-García, R. ; Bonaguro, L.DZNE* ; Brumhard, S. ; Michalick, L. ; Lippert, L. J. ; Kostevc, T. ; Gäbel, C. ; Schneider, M. ; Streitz, M. ; Demichev, V. ; Gemünd, I. D.Extern* ; Barone, M. ; Tober-Lau, P. ; Helbig, E. T. ; Hillus, D. ; Petrov, L. ; Stein, J. ; Dey, H.-P. ; Paclik, D. ; Iwert, C. ; Mülleder, M. ; Aulakh, S. K. ; Djudjaj, S. ; Bülow, R. D. ; Mei, H. E. ; Schulz, A. R. ; Thiel, A. ; Hippenstiel, S. ; Saliba, A.-E. ; Eils, R. ; Lehmann, I. ; Mall, M. A. ; Stricker, S. ; Röhmel, J. ; Corman, V.Extern* ; Beule, D. ; Wyler, E. ; Landthaler, M. ; Obermayer, B. ; von Stillfried, S. ; Boor, P. ; Demir, M. ; Wesselmann, H. ; Suttorp, N. ; Uhrig, A. ; Müller-Redetzky, H. ; Nattermann, J. ; Kuebler, W. M. ; Meisel, C. ; Ralser, M. ; Schultze, J. L.DZNE* ; Aschenbrenner, A. C.DZNE* ; Thibeault, C. ; Kurth, F. ; Sander, L. E. ; Blüthgen, N. ; Sawitzki, B. ; Group, P. S. (Collaboration Author)

2022
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.cell.2021.12.040

Abstract: Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. Proportions of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; COVID-19: immunology (MeSH) ; COVID-19: pathology (MeSH) ; COVID-19: virology (MeSH) ; Chemotactic Factors: metabolism (MeSH) ; Complement Activation (MeSH) ; Cytotoxicity, Immunologic (MeSH) ; Endothelial Cells: virology (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Lymphocyte Activation (MeSH) ; Male (MeSH) ; Microvessels: virology (MeSH) ; Middle Aged (MeSH) ; Monocytes: metabolism (MeSH) ; Neutrophils: metabolism (MeSH) ; Proteome (MeSH) ; Receptors, IgG: metabolism (MeSH) ; SARS-CoV-2: immunology (MeSH) ; Single-Cell Analysis (MeSH) ; T-Lymphocytes, Cytotoxic: immunology (MeSH) ; Transcriptome (MeSH) ; Young Adult (MeSH) ; COVID-19 ; T cells ; complement ; cytotoxicity ; immunopathology ; Chemotactic Factors ; Proteome ; Receptors, IgG

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Contributing Institute(s):

1. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)
2. Platform for Single Cell Genomics and Epigenomics at DZNE & University of Bonn (R&D PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Georg, P. ; Astaburuaga-García, R. ; Bonaguro, L.DZNE* ; Blüthgen, N. ; Sawitzki, B.
Dataset: Complement activation induces excessive T cell cytotoxicity in severe COVID-19: Analysis of single cell data cohort 1 (Berlin), v1.0.0
Zenodo (2021) [10.5281/zenodo.5771936]2021 BibTeX | EndNote: XML, Text | RIS

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