Meckiff, Benjamin J, Ramirez-Suastegui, Ciro, Fajardo, Vicente, Chee, Serena J, Kusnadi, Anthony, Simon, Hayley, Eschweiler, Simon, Grifoni, Alba, Pelosi, Emanuela, Weiskopf, Daniela et al (show 5 more authors)
(2020)
Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19.
Cell, 183 (5).
pp. 1340-1353.
Abstract
The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (TH) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional TH1 and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities.
Item Type: | Article |
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Uncontrolled Keywords: | T-Lymphocytes, Cytotoxic, Humans, Antibodies, Viral, CD4 Lymphocyte Count, Severity of Illness Index, Cohort Studies, Reverse Transcriptase Polymerase Chain Reaction, Adult, Aged, Aged, 80 and over, Middle Aged, England, Female, Male, T-Lymphocytes, Regulatory, Single-Cell Analysis, Transcriptome, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2, T Follicular Helper Cells |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 12 Jul 2021 09:44 |
Last Modified: | 18 Jan 2023 21:36 |
DOI: | 10.1016/j.cell.2020.10.001 |
Open Access URL: | https://eprints.soton.ac.uk/444594/ |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3129736 |