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DOI 10.1016/j.cell.2021.12.040

Медицинская библиотека · Cell · 2021

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

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, PA-COVID-19 Study Group

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Аннотация

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.

Для цитирования: 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, PA-COVID-19 Study Group. Complement activation induces excessive T cell cytotoxicity in severe COVID-19.. Cell. 2021. DOI: 10.1016/j.cell.2021.12.040.

Предметные рубрики MeSH

AdultAgedAged, 80 and overCOVID-19Chemotactic FactorsComplement ActivationCytotoxicity, ImmunologicEndothelial CellsFemaleHumansLymphocyte ActivationMaleMicrovesselsMiddle AgedMonocytesNeutrophilsProteomeReceptors, IgGSARS-CoV-2Single-Cell AnalysisT-Lymphocytes, CytotoxicTranscriptomeYoung Adult
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