Author: Georg, P.; Astaburuaga-Garcia, R.; Bonaguro, L.; Brumhard, S.; Michalick, L.; Lippert, L. J.; Kostevc, T.; Gäbel, C.; Schneider, M.; Streitz, M.; Demichev, V.; Gemünd, I.; Barone, M.; Tober-Lau, P.; Helbig, E. T.; Stein, J.; Dey, H.-P.; Paclik, D.; Mülleder, M.; Aulakh, S. K.; Mei, H. E.; Schulz, A. R.; Hippenstiel, S.; Corman, V. M.; Beule, D.; Wyler, E.; Landthaler, M.; Obermayer-Wasserscheid, B.; Boor, P.; Demir, M.; Wesselmann, H.; Suttorp, N.; Uhrig, A.; Müller-Redetzky, H.; Nattermann, J.; Kuebler, W. M.; Meisel, C.; Ralser, M.; Schultze, J. L.; Aschenbrenner, A. C.; Thibeault, C.
Title: Complement activation induces excessive T cell cytotoxicity in severe COVID-19 Cord-id: koj3hjg9 Document date: 2021_6_11
ID: koj3hjg9
Snippet: 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, CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent deg
Document: 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, 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.
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