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

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved..

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.

Errataetall:

UpdateOf: bioRxiv. 2020 Jun 13;:. - PMID 32587963

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:183

Enthalten in:

Cell - 183(2020), 5 vom: 25. Nov., Seite 1340-1353.e16

Sprache:

Englisch

Beteiligte Personen:

Meckiff, Benjamin J [VerfasserIn]
Ramírez-Suástegui, Ciro [VerfasserIn]
Fajardo, Vicente [VerfasserIn]
Chee, Serena J [VerfasserIn]
Kusnadi, Anthony [VerfasserIn]
Simon, Hayley [VerfasserIn]
Eschweiler, Simon [VerfasserIn]
Grifoni, Alba [VerfasserIn]
Pelosi, Emanuela [VerfasserIn]
Weiskopf, Daniela [VerfasserIn]
Sette, Alessandro [VerfasserIn]
Ay, Ferhat [VerfasserIn]
Seumois, Grégory [VerfasserIn]
Ottensmeier, Christian H [VerfasserIn]
Vijayanand, Pandurangan [VerfasserIn]

Links:

Volltext

Themen:

ARTE
Antibodies, Viral
Antigen-reactive T cell enrichment
CD4(+) T cells
CD4-CTLs
COVID-19
Cytotoxic
Human
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
SARS-CoV-2
ScRNA-seq
Single-cell RNA sequencing
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2
T(FH)
T(REG)

Anmerkungen:

Date Completed 11.12.2020

Date Revised 10.02.2024

published: Print-Electronic

UpdateOf: bioRxiv. 2020 Jun 13;:. - PMID 32587963

Citation Status MEDLINE

doi:

10.1016/j.cell.2020.10.001

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM316648876