CD8 + T cells reactive to influenza and respiratory syncytial virus from healthy participants displayed polyfunctional features and enhanced glycolysis. In contrast, SARS-CoV-2–reactive cells in the dominant nonexhausted subset from patients with severe disease showed enrichment of transcripts linked to costimulation, prosurvival NF-κB signaling, and antiapoptotic pathways, suggesting the generation of robust CD8 + T cell memory responses in patients with severe COVID-19 illness. Patients with COVID-19 were segregated into two groups based on whether the dominant CD8 + T cell response to SARS-CoV-2 was “exhausted” or “non-exhausted.” SARS-CoV-2–reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in patients with COVID-19 experiencing mild compared with severe illness. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 + T cells, obtained using a modified antigen-reactive T cell enrichment assay, from 39 patients with COVID-19 and 10 healthy participants.
The molecular properties of CD8 + T cells that respond to SARS-CoV-2 infection are not fully known.
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