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| Item Type: | Article | ||||
|---|---|---|---|---|---|
| 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 Hillus, D. and Petrov, L. and Stein, J. and Dey, H.P. and Paclik, D. and Iwert, C. and Mülleder, M. and Aulakh, S.K. and Djudjaj, S. and Bülow, R.D. and Mei, H.E. and Schulz, A.R. and Thiel, A. and Hippenstiel, S. and Saliba, A.E. and Eils, R. and Lehmann, I. and Mall, M.A. and Stricker, S. and Röhmel, J. and Corman, V.M. and Beule, D. and Wyler, E. and Landthaler, M. and Obermayer, B. and von Stillfried, S. 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 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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