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

2020; Cell Press; Volume: 183; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2020.10.001

1097-4172

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

Immune responses and vaccinations

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.