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

Area of Science:

• Immunology
• Pathology
• Molecular Biology

Background:

• Severe COVID-19 presents with immune dysregulation and pathology.
• The specific role of T cells in COVID-19 pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the function and regulation of pathogenic T cells in severe COVID-19.
• To identify T cell subsets contributing to COVID-19 disease severity.

Main Methods:

• Combined single-cell transcriptomics and proteomics.
• Mechanistic studies of T cell functions.
• Analysis of immune cell interactions and complement system activation.

Main Results:

• Identified highly activated CD16+ T cells with enhanced cytotoxic functions in severe COVID-19.
• Demonstrated CD16-mediated, T cell receptor-independent cytotoxicity and endothelial cell injury.
• Found that C3a generation in severe COVID-19 induces CD16+ cytotoxic T cells.
• Observed association between CD16+ T cells, complement activation, and fatal COVID-19 outcomes.

Conclusions:

• CD16+ T cells exhibit unique pathogenic functions in severe COVID-19.
• Exacerbated T cell cytotoxicity and complement activation play a significant role in COVID-19 mortality.