Selected Grantee Publications

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

Meckiff  et al., Cell. 2020.

https://pubmed.ncbi.nlm.nih.gov/33096020/

It is not clear why COVID-19 is deadly in some people and mild in others. To understand the underlying mechanism, investigators studied the contribution of CD4⁺ T cells in immune responses to SARS-CoV-2 infection. They analyzed single-cell transcriptomic data of >100,000 viral antigen-reactive CD4⁺ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, they found increased proportions of cytotoxic follicular helper cells (TFH) and cytotoxic T helper (TH) cells 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, these analyses provided insights into the gene expression patterns of SARS-CoV-2-reactive CD4⁺ T cells in distinct disease severities. Supported by ORIP (S10RR027366, S10OD025052), NIAID, NHLBI, and NIGMS.