Complement activation induces excessive T cell cytotoxicity in severe COVID-19.
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Authors
Georg, PhilippAstaburuaga-García, Rosario
Bonaguro, Lorenzo
Brumhard, Sophia
Michalick, Laura
Lippert, Lena J
Kostevc, Tomislav
Gäbel, Christiane
Schneider, Maria
Streitz, Mathias
Demichev, Vadim
Gemünd, Ioanna
Barone, Matthias
Tober-Lau, Pinkus
Helbig, Elisa T
Hillus, David
Petrov, Lev
Stein, Julia
Dey, Hannah-Philine
Paclik, Daniela
Iwert, Christina
Mülleder, Michael
Aulakh, Simran Kaur
Djudjaj, Sonja
Bülow, Roman D
Mei, Henrik E
Schulz, Axel R
Thiel, Andreas
Hippenstiel, Stefan
Saliba, Antoine-Emmanuel
Eils, Roland
Lehmann, Irina
Mall, Marcus A
Stricker, Sebastian
Röhmel, Jobst
Corman, Victor M
Beule, Dieter
Wyler, Emanuel
Landthaler, Markus
Obermayer, Benedikt
von Stillfried, Saskia
Boor, Peter
Demir, Münevver
Wesselmann, Hans
Suttorp, Norbert
Uhrig, Alexander
Müller-Redetzky, Holger
Nattermann, Jacob
Kuebler, Wolfgang M
Meisel, Christian
Ralser, Markus
Schultze, Joachim L
Aschenbrenner, Anna C
Thibeault, Charlotte
Kurth, Florian
Sander, Leif E
Blüthgen, Nils
Sawitzki, Birgit
Issue Date
2021-12-28
Metadata
Show full item recordAbstract
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.Citation
Cell. 2022 Feb 3;185(3):493-512.e25. doi: 10.1016/j.cell.2021.12.040. Epub 2021 Dec 28. PMID: 35032429.Affiliation
HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.Publisher
ElsevierJournal
CellPubMed ID
35032429Type
ArticleLanguage
enEISSN
1097-4172ae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2021.12.040
Scopus Count
The following license files are associated with this item:
- Creative Commons
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