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 H 1 and T H 17 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. Graphical Abstract Analyses of CD4 + T cells from 40 COVID-19 patients show that hospitalization is associated with increased cytotoxic follicular helper cells and cytotoxic T helper cells and a reduction in regulatory T cells.
【저자키워드】 COVID-19, SARS-CoV-2, Human, Single-cell RNA sequencing, scRNA-seq, CD4+ T cells, cytotoxic, Treg, antigen-reactive T cell enrichment, TFH, ARTE, CD4-CTLs,