%0 Journal Article
%A Georg, Philipp
%A Astaburuaga-García, Rosario
%A Bonaguro, Lorenzo
%A Brumhard, Sophia
%A Michalick, Laura
%A Lippert, Lena J
%A Kostevc, Tomislav
%A Gäbel, Christiane
%A Schneider, Maria
%A Streitz, Mathias
%A Demichev, Vadim
%A Gemünd, Ioanna Dafni
%A Barone, Matthias
%A Tober-Lau, Pinkus
%A Helbig, Elisa T
%A Hillus, David
%A Petrov, Lev
%A Stein, Julia
%A Dey, Hannah-Philine
%A Paclik, Daniela
%A Iwert, Christina
%A Mülleder, Michael
%A Aulakh, Simran Kaur
%A Djudjaj, Sonja
%A Bülow, Roman D
%A Mei, Henrik E
%A Schulz, Axel R
%A Thiel, Andreas
%A Hippenstiel, Stefan
%A Saliba, Antoine-Emmanuel
%A Eils, Roland
%A Lehmann, Irina
%A Mall, Marcus A
%A Stricker, Sebastian
%A Röhmel, Jobst
%A Corman, Victor
%A Beule, Dieter
%A Wyler, Emanuel
%A Landthaler, Markus
%A Obermayer, Benedikt
%A von Stillfried, Saskia
%A Boor, Peter
%A Demir, Münevver
%A Wesselmann, Hans
%A Suttorp, Norbert
%A Uhrig, Alexander
%A Müller-Redetzky, Holger
%A Nattermann, Jacob
%A Kuebler, Wolfgang M
%A Meisel, Christian
%A Ralser, Markus
%A Schultze, Joachim L
%A Aschenbrenner, Anna C
%A Thibeault, Charlotte
%A Kurth, Florian
%A Sander, Leif E
%A Blüthgen, Nils
%A Sawitzki, Birgit
%T Complement activation induces excessive T cell cytotoxicity in severe COVID-19.
%J Cell
%V 185
%N 3
%@ 0092-8674
%C New York, NY
%I Elsevier
%M DZNE-2022-00698
%P 493 - 512.e25
%D 2022
%X 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.
%K Adult
%K Aged
%K Aged, 80 and over
%K COVID-19: immunology
%K COVID-19: pathology
%K COVID-19: virology
%K Chemotactic Factors: metabolism
%K Complement Activation
%K Cytotoxicity, Immunologic
%K Endothelial Cells: virology
%K Female
%K Humans
%K Lymphocyte Activation
%K Male
%K Microvessels: virology
%K Middle Aged
%K Monocytes: metabolism
%K Neutrophils: metabolism
%K Proteome
%K Receptors, IgG: metabolism
%K SARS-CoV-2: immunology
%K Single-Cell Analysis
%K T-Lymphocytes, Cytotoxic: immunology
%K Transcriptome
%K Young Adult
%K COVID-19 (Other)
%K T cells (Other)
%K complement (Other)
%K cytotoxicity (Other)
%K immunopathology (Other)
%K Chemotactic Factors (NLM Chemicals)
%K Proteome (NLM Chemicals)
%K Receptors, IgG (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35032429
%2 pmc:PMC8712270
%R 10.1016/j.cell.2021.12.040
%U https://pub.dzne.de/record/164035