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dc.contributor.authorGeorg, Philipp
dc.contributor.authorAstaburuaga-García, Rosario
dc.contributor.authorBonaguro, Lorenzo
dc.contributor.authorBrumhard, Sophia
dc.contributor.authorMichalick, Laura
dc.contributor.authorLippert, Lena J
dc.contributor.authorKostevc, Tomislav
dc.contributor.authorGäbel, Christiane
dc.contributor.authorSchneider, Maria
dc.contributor.authorStreitz, Mathias
dc.contributor.authorDemichev, Vadim
dc.contributor.authorGemünd, Ioanna
dc.contributor.authorBarone, Matthias
dc.contributor.authorTober-Lau, Pinkus
dc.contributor.authorHelbig, Elisa T
dc.contributor.authorHillus, David
dc.contributor.authorPetrov, Lev
dc.contributor.authorStein, Julia
dc.contributor.authorDey, Hannah-Philine
dc.contributor.authorPaclik, Daniela
dc.contributor.authorIwert, Christina
dc.contributor.authorMülleder, Michael
dc.contributor.authorAulakh, Simran Kaur
dc.contributor.authorDjudjaj, Sonja
dc.contributor.authorBülow, Roman D
dc.contributor.authorMei, Henrik E
dc.contributor.authorSchulz, Axel R
dc.contributor.authorThiel, Andreas
dc.contributor.authorHippenstiel, Stefan
dc.contributor.authorSaliba, Antoine-Emmanuel
dc.contributor.authorEils, Roland
dc.contributor.authorLehmann, Irina
dc.contributor.authorMall, Marcus A
dc.contributor.authorStricker, Sebastian
dc.contributor.authorRöhmel, Jobst
dc.contributor.authorCorman, Victor M
dc.contributor.authorBeule, Dieter
dc.contributor.authorWyler, Emanuel
dc.contributor.authorLandthaler, Markus
dc.contributor.authorObermayer, Benedikt
dc.contributor.authorvon Stillfried, Saskia
dc.contributor.authorBoor, Peter
dc.contributor.authorDemir, Münevver
dc.contributor.authorWesselmann, Hans
dc.contributor.authorSuttorp, Norbert
dc.contributor.authorUhrig, Alexander
dc.contributor.authorMüller-Redetzky, Holger
dc.contributor.authorNattermann, Jacob
dc.contributor.authorKuebler, Wolfgang M
dc.contributor.authorMeisel, Christian
dc.contributor.authorRalser, Markus
dc.contributor.authorSchultze, Joachim L
dc.contributor.authorAschenbrenner, Anna C
dc.contributor.authorThibeault, Charlotte
dc.contributor.authorKurth, Florian
dc.contributor.authorSander, Leif E
dc.contributor.authorBlüthgen, Nils
dc.contributor.authorSawitzki, Birgit
dc.date.accessioned2022-03-29T14:38:50Z
dc.date.available2022-03-29T14:38:50Z
dc.date.issued2021-12-28
dc.identifier.citationCell. 2022 Feb 3;185(3):493-512.e25. doi: 10.1016/j.cell.2021.12.040. Epub 2021 Dec 28. PMID: 35032429.en_US
dc.identifier.pmid35032429
dc.identifier.doi10.1016/j.cell.2021.12.040
dc.identifier.urihttp://hdl.handle.net/10033/623170
dc.description.abstractSevere 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.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCOVID-19en_US
dc.subjectT cellsen_US
dc.subjectcomplementen_US
dc.subjectcytotoxicityen_US
dc.subjectimmunopathologyen_US
dc.titleComplement activation induces excessive T cell cytotoxicity in severe COVID-19.en_US
dc.typeArticleen_US
dc.identifier.eissn1097-4172
dc.contributor.departmentHIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany.en_US
dc.identifier.journalCellen_US
dc.source.volume185
dc.source.issue3
dc.source.beginpage493
dc.source.endpage512.e25
refterms.dateFOA2022-03-29T14:38:51Z
dc.source.journaltitleCell
dc.source.countryUnited Kingdom
dc.source.countryUnited Kingdom
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International