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

Cell. 2020 Nov 25;183(5):1340-1353.e16. doi: 10.1016/j.cell.2020.10.001. Epub 2020 Oct 5.

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.

Keywords: ARTE; CD4(+) T cells; CD4-CTLs; COVID-19; SARS-CoV-2; T(FH); T(REG); antigen-reactive T cell enrichment; cytotoxic; human; scRNA-seq; single-cell RNA sequencing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't