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

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Kusnadi, Anthony, Ramirez-Suastegui, Ciro, Fajardo, Vicente, Chee, Serena J, Meckiff, Benjamin J, Simon, Hayley, Pelosi, Emanuela, Seumois, Gregory, Ay, Ferhat, Vijayanand, Pandurangan et al (show 1 more authors) (2021) Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells. SCIENCE IMMUNOLOGY, 6 (55). eabe4782-. ISSN 2470-9468, 2470-9468

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Official URL: https://doi.org/10.1126/sciimmunol.abe4782

Abstract

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 non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB 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.

Item Type:	Article
Uncontrolled Keywords:	CD8-Positive T-Lymphocytes, Humans, NF-kappa B, Signal Transduction, Immunologic Memory, Glycolysis, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Single-Cell Analysis, COVID-19, SARS-CoV-2
Depositing User:	Symplectic Admin
Date Deposited:	18 Feb 2021 11:12
Last Modified:	07 Dec 2024 11:14
DOI:	10.1126/sciimmunol.abe4782
Open Access URL:	https://doi.org/10.1126/sciimmunol.abe4782
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3115812