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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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