Back to Search Start Over

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Authors :
Philipp Georg
Rosario Astaburuaga-García
Lorenzo Bonaguro
Sophia Brumhard
Laura Michalick
Lena J. Lippert
Tomislav Kostevc
Christiane Gäbel
Maria Schneider
Mathias Streitz
Vadim Demichev
Ioanna Gemünd
Matthias Barone
Pinkus Tober-Lau
Elisa Theresa Helbig
Julia Stein
Hannah-Philine Dey
Daniela Paclik
Michael Mülleder
Simran Kaur Aulakh
Henrik E. Mei
Axel R. Schulz
Stefan Hippenstiel
Victor Max Corman
Dieter Beule
Emanuel Wyler
Markus Landthaler
Benedikt Obermayer-Wasserscheid
Peter Boor
Münevver Demir
Hans Wesselmann
Norbert Suttorp
Alexander Uhrig
Holger Müller-Redetzky
Jacob Nattermann
Wolfgang M. Kuebler
Christian Meisel
Markus Ralser
Joachim L. Schultze
Anna C. Aschenbrenner
Charlotte Thibeault
Florian Kurth
Leif-Erik Sander
Nils Blüthgen
Birgit Sawitzki
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

SummarySevere COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and 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. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........89aba5a5afc97e368ed42a3c27691dcb
Full Text :
https://doi.org/10.1101/2021.06.08.21258481