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

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 func...

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Detalles Bibliográficos
Autores principales: Georg, Philipp, Astaburuaga-García, Rosario, Bonaguro, Lorenzo, Brumhard, Sophia, Michalick, Laura, Lippert, Lena J., Kostevc, Tomislav, Gäbel, Christiane, Schneider, Maria, Streitz, Mathias, Demichev, Vadim, Gemünd, Ioanna, Barone, Matthias, Tober-Lau, Pinkus, Helbig, Elisa T., Hillus, David, Petrov, Lev, Stein, Julia, Dey, Hannah-Philine, Paclik, Daniela, Iwert, Christina, Mülleder, Michael, Aulakh, Simran Kaur, Djudjaj, Sonja, Bülow, Roman D., Mei, Henrik E., Schulz, Axel R., Thiel, Andreas, Hippenstiel, Stefan, Saliba, Antoine-Emmanuel, Eils, Roland, Lehmann, Irina, Mall, Marcus A., Stricker, Sebastian, Röhmel, Jobst, Corman, Victor M., Beule, Dieter, Wyler, Emanuel, Landthaler, Markus, Obermayer, Benedikt, von Stillfried, Saskia, Boor, Peter, Demir, Münevver, Wesselmann, Hans, Suttorp, Norbert, Uhrig, Alexander, Müller-Redetzky, Holger, Nattermann, Jacob, Kuebler, Wolfgang M., Meisel, Christian, Ralser, Markus, Schultze, Joachim L., Aschenbrenner, Anna C., Thibeault, Charlotte, Kurth, Florian, Sander, Leif E., Blüthgen, Nils, Sawitzki, Birgit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712270/
https://www.ncbi.nlm.nih.gov/pubmed/35032429
http://dx.doi.org/10.1016/j.cell.2021.12.040
Descripción
Sumario: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.