Complement activation induces excessive T cell cytotoxicity in severe COVID-19
Authors:
- Georg, Philipp
- Astaburuaga-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
Details:
Cell, Volume 185, Issue 3, 2022-02-03
Article Link: Click here
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.