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

Item Type:Preprint
Title:Complement activation induces excessive T cell cytotoxicity in severe COVID-19
Creators Name:Georg, P. and Astaburuaga-García, R. and Bonaguro, L. and Brumhard, S. and Michalick, L. and Lippert, L.J. and Kostevc, T. and Gäbel, C. and Schneider, M. and Streitz, M. and Demichev, V. and Gemünd, I. and Barone, M. and Tober-Lau, P. and Helbig, E.T. and Stein, J. and Dey, H.P. and Paclik, D. and Mülleder, M. and Aulakh, S.K. and Mei, H.E. and Schulz, A.R. and Hippenstiel, S. and Corman, V.M. and Beule, D. and Wyler, E. and Landthaler, M. and Obermayer-Wasserscheid, B. and Boor, P. and Demir, M. and Wesselmann, H. and Suttorp, N. and Uhrig, A. and Müller-Redetzky, H. and Nattermann, J. and Kuebler, W.M. and Meisel, C. and Ralser, M. and Schultze, J.L. and Aschenbrenner, A.C. and Thibeault, C. and Kurth, F. and Sander, L.E. and Blüthgen, N. and Sawitzki, B.
Abstract:Severe 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, CD(16+) 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. CD(16+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD(16+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Age-dependent generation of C3a in severe COVID-19 induced activated CD(16+) cytotoxic T cells. The proportion of activated CD(16+) 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.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2021.06.08.21258481
Date:11 June 2021
Official Publication:https://doi.org/10.1101/2021.06.08.21258481
Related to:
https://edoc.mdc-berlin.de/21230/Final version

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