Paper of the Month
DEZEMBER 2021 - Die fatale Rolle der T-Zellen bei COVID-19
Im Dezember 2021 erhielt Birgit Sawitzki die Auszeichnung Paper of the Month.
Publikation
Georg P, Astaburuaga-García R, Bonaguro L, Brumhard S, Michalick L, Lippert LJ, Kostevc T, Gäbel C, Schneider M, Streitz M, Demichev V, Gemünd I, Barone M, Tober-Lau P, Helbig ET, Hillus D, Petrov L, Stein J, Dey HP, Paclik D, Iwert C, Mülleder M, Aulakh SK, Djudjaj S, Bülow RD, Mei HE, Schulz AR, Thiel A, Hippenstiel S, Saliba AE, Eils R, Lehmann I, Mall MA, Stricker S, Röhmel J, Corman VM, 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 WM, Meisel C, Ralser M, Schultze JL, Aschenbrenner AC, Thibeault C, Kurth F, Sander LE, Blüthgen N, Sawitzki B; PA-COVID-19 Study Group. Complement activation induces excessive T cell cytotoxicity in severe COVID-19. Cell. 2022 Feb 3;185(3):493-512.e25. doi: 10.1016/j.cell.2021.12.040. Epub 2021 Dec 28. PMID: 35032429; PMCID: PMC8712270.
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.
