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

Georg, P.; Astaburuaga-García, 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.; Hillus, D.; Petrov, L.; Stein, J.; Dey, H.P.; Paclik, D.; Iwert, C.; Mülleder, M.; Aulakh, S.K.; Djudjaj, S.; Bülow, R.D.; Mei, H.E.; Schulz, A.R.; Thiel, A.; Hippenstiel, S.; Saliba, A.E.; Eils, R.; Lehmann, I.; Mall, M.A.; Stricker, S.; Röhmel, J.; Corman, V.M.; Beule, D.; Wyler, E.; Landthaler, M.; Obermayer, B.; von Stillfried, S.; 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.; Kurth, F.; Sander, L.E.; Blüthgen, N.; Sawitzki, B.

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

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Item Type:	Article
Title:	Complement activation induces excessive T cell cytotoxicity in severe COVID-19
Creators Name:	Georg, P., Astaburuaga-García, 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., Hillus, D., Petrov, L., Stein, J., Dey, H.P., Paclik, D., Iwert, C., Mülleder, M., Aulakh, S.K., Djudjaj, S., Bülow, R.D., Mei, H.E., Schulz, A.R., Thiel, A., Hippenstiel, S., Saliba, A.E., Eils, R., Lehmann, I., Mall, M.A., Stricker, S., Röhmel, J., Corman, V.M., Beule, D., Wyler, E., Landthaler, M., Obermayer, B., von Stillfried, S., 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., Kurth, F., Sander, L.E., Blüthgen, N. and Sawitzki, B.
Abstract:	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.
Keywords:	COVID-19, T Cells, Complement, Cytotoxicity, Immunopathology
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	185
Number:	3
Page Range:	493-512
Date:	3 February 2022
Official Publication:	https://doi.org/10.1016/j.cell.2021.12.040
PubMed:	View item in PubMed

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