Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19

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.

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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
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
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