TY  - JOUR
AU  - Georg, Philipp
AU  - Astaburuaga-García, Rosario
AU  - Bonaguro, Lorenzo
AU  - Brumhard, Sophia
AU  - Michalick, Laura
AU  - Lippert, Lena J
AU  - Kostevc, Tomislav
AU  - Gäbel, Christiane
AU  - Schneider, Maria
AU  - Streitz, Mathias
AU  - Demichev, Vadim
AU  - Gemünd, Ioanna Dafni
AU  - Barone, Matthias
AU  - Tober-Lau, Pinkus
AU  - Helbig, Elisa T
AU  - Hillus, David
AU  - Petrov, Lev
AU  - Stein, Julia
AU  - Dey, Hannah-Philine
AU  - Paclik, Daniela
AU  - Iwert, Christina
AU  - Mülleder, Michael
AU  - Aulakh, Simran Kaur
AU  - Djudjaj, Sonja
AU  - Bülow, Roman D
AU  - Mei, Henrik E
AU  - Schulz, Axel R
AU  - Thiel, Andreas
AU  - Hippenstiel, Stefan
AU  - Saliba, Antoine-Emmanuel
AU  - Eils, Roland
AU  - Lehmann, Irina
AU  - Mall, Marcus A
AU  - Stricker, Sebastian
AU  - Röhmel, Jobst
AU  - Corman, Victor
AU  - Beule, Dieter
AU  - Wyler, Emanuel
AU  - Landthaler, Markus
AU  - Obermayer, Benedikt
AU  - von Stillfried, Saskia
AU  - Boor, Peter
AU  - Demir, Münevver
AU  - Wesselmann, Hans
AU  - Suttorp, Norbert
AU  - Uhrig, Alexander
AU  - Müller-Redetzky, Holger
AU  - Nattermann, Jacob
AU  - Kuebler, Wolfgang M
AU  - Meisel, Christian
AU  - Ralser, Markus
AU  - Schultze, Joachim L
AU  - Aschenbrenner, Anna C
AU  - Thibeault, Charlotte
AU  - Kurth, Florian
AU  - Sander, Leif E
AU  - Blüthgen, Nils
AU  - Sawitzki, Birgit
TI  - Complement activation induces excessive T cell cytotoxicity in severe COVID-19.
JO  - Cell
VL  - 185
IS  - 3
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2022-00698
SP  - 493 - 512.e25
PY  - 2022
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - COVID-19: immunology
KW  - COVID-19: pathology
KW  - COVID-19: virology
KW  - Chemotactic Factors: metabolism
KW  - Complement Activation
KW  - Cytotoxicity, Immunologic
KW  - Endothelial Cells: virology
KW  - Female
KW  - Humans
KW  - Lymphocyte Activation
KW  - Male
KW  - Microvessels: virology
KW  - Middle Aged
KW  - Monocytes: metabolism
KW  - Neutrophils: metabolism
KW  - Proteome
KW  - Receptors, IgG: metabolism
KW  - SARS-CoV-2: immunology
KW  - Single-Cell Analysis
KW  - T-Lymphocytes, Cytotoxic: immunology
KW  - Transcriptome
KW  - Young Adult
KW  - COVID-19 (Other)
KW  - T cells (Other)
KW  - complement (Other)
KW  - cytotoxicity (Other)
KW  - immunopathology (Other)
KW  - Chemotactic Factors (NLM Chemicals)
KW  - Proteome (NLM Chemicals)
KW  - Receptors, IgG (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35032429
C2  - pmc:PMC8712270
DO  - DOI:10.1016/j.cell.2021.12.040
UR  - https://pub.dzne.de/record/164035
ER  -