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

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 (T_H) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (T_REG). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic T_FH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional T_H1 and T_H17 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.

SUBMITTER: Meckiff BJ

PROVIDER: S-EPMC7534589 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Meckiff Benjamin J BJ Ramírez-Suástegui Ciro C Fajardo Vicente V Chee Serena J SJ Kusnadi Anthony A Simon Hayley H Eschweiler Simon S Grifoni Alba A Pelosi Emanuela E Weiskopf Daniela D Sette Alessandro A Ay Ferhat F Seumois Grégory G Ottensmeier Christian H CH Vijayanand Pandurangan P

Cell 20201005 5

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 propor ...[more]

PMID: 33096020

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Project description:We examined the relationship between peripheral blood levels of SARS-CoV-2 S (Spike protein)1/M (Membrane protein)-reactive IFN-γ-producing CD4+ and CD8+ T cells, serum levels of biomarkers of clinical severity, and mortality in critically ill COVID-19 patients. The potential association between SARS-CoV-2-S-Receptor Binding Domain (RBD)-specific IgG levels in sera and mortality was also investigated. SARS-CoV-2 T cells and anti-RBD IgG levels were monitored in 71 non-consecutive patients (49 male and 22 female; median age, 65 years) by whole-blood flow cytometry and Enzyme-linked immunosorbent assay (ELISA), respectively (326 specimens). SARS-CoV-2 RNA loads in paired tracheal aspirates [TA] (n = 147) were available from 54 patients. Serum levels of interleukin-6, ferritin, D-Dimer, lactose dehydrogenase and C-reactive protein in paired sera were known. SARS-CoV-2 T cells (either CD4+, CD8+ or both) were detectable in 70 patients. SARS-CoV-2 IFN-γ CD4+ T-cell responses were documented more frequently than their CD8+ counterparts (62 vs. 56 patients) and were of greater magnitude overall. Detectable SARS-CoV-2 S1/M-reactive CD8+ and CD4+ T-cell responses were associated with higher SARS-CoV-2 RNA loads in TA. SARS-CoV-2 RNA load in TA decreased over time, irrespective of the dynamics of SARS-CoV-2-reactive CD8+ and CD4+ T cells. No correlation was found between SARS-CoV-2 IFN-γ T-cell counts, anti-RBD IgG concentrations and biomarker serum levels (Rho ≤ 0.3). The kinetics of both T cell subsets was comparable between those who died or survived, whereas anti-RBD IgG levels were higher across different time points in deceased patients than in survivors. Enumeration of peripheral blood levels of SARS-CoV-2-S1/M-reactive IFN-γ CD4+ and CD8+ T cells does not predict viral clearance from the lower respiratory tract or poor clinical outcomes in critically ill COVID-19 patients. In contrast, anti-RBD IgG levels were directly associated with increased mortality.

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

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Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4<sup>+</sup> T Cells in COVID-19.

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Dataset Information

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

Publications

Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4&lt;sup&gt;+&lt;/sup&gt; T Cells in COVID-19.

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OmicsDI is part of the ELIXIR infrastructure

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

Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4<sup>+</sup> T Cells in COVID-19.