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Complement activation induces excessive T cell cytotoxicity in severe COVID-19
- Publication Year :
- 2021
- Publisher :
- Cold Spring Harbor Laboratory, 2021.
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Abstract
- SummarySevere COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathogenesis, and it remains unclear if T cells also contribute to disease pathology. Here, we combined single-cell transcriptomics and 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. Age-dependent generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. The proportion of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a correlated with clinical outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.
- Subjects :
- chemical and pharmacologic phenomena
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........89aba5a5afc97e368ed42a3c27691dcb
- Full Text :
- https://doi.org/10.1101/2021.06.08.21258481