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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
Georg, Philipp
Astaburuaga-García, Rosario
Bonaguro, Lorenzo
Brumhard, Sophia
Michalick, Laura
Lippert, Lena J
Kostevc, Tomislav
Gäbel, Christiane
Schneider, Maria
Streitz, Mathias
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2021-12-28
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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.
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Cell. 2022 Feb 3;185(3):493-512.e25. doi: 10.1016/j.cell.2021.12.040. Epub 2021 Dec 28. PMID: 35032429.
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en
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1097-4172
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Attribution 4.0 International