4.7 Article

Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8(+) T cells

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SCIENCE IMMUNOLOGY
卷 6, 期 55, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abe4782

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资金

  1. NIH [U19AI142742, U19AI118626, R01HL114093, R35GM128938, S10RR027366, S10OD025052]
  2. William K. Bowes Jr Foundation
  3. Whittaker foundation
  4. Wessex Clinical Research Network
  5. National Institute of Health Research UK

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CD8(+) T cells in COVID-19 patients exhibit two distinct states – exhausted and non-exhausted, with non-exhausted cells in severe cases showing enhanced memory responses to SARS-CoV-2 infection.
The molecular properties of CD8(+) T cells that respond to SARS-CoV-2 infection are not fully known. 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 (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8(+) T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant nonexhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-kappa B signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8(+) T cell memory responses in patients with severe COVID-19 illness. CD8(+) T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8(+) T cells responding to SARS-CoV-2.

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