A collaboration of multiple research institutions reveals the cellular activation states of SARS-CoV-2 reactive T cells in the lung and blood. The study was published in Nature Communications.
The response of T lymphocytes plays a critical role in the immune system's fight against SARS-CoV-2, which is a consensus in the scientific and medical communities. But what is the state of antigen-reactive T cells at different sites in the body of COVID-19 patients? And which gene expression changes do they undergo during the course of disease? Little is known about this.
To answer these questions, the researchers applied a new methodological trick, `reverse phenotyping', based on single-cell analyses of reactive T-cell receptors. Using the reverse phenotyping and integration of this data with single cell RNA-seq data sets obtained from respiratory material from several patient cohorts, it was possible for the first time to determine how the activity state of SARS-COV-2 reactive T cells in the lung changes during the course of the disease. This revealed how SARS-CoV-2 reactive T cell clones differ in the acute phase of infection (with virus still detectable) versus the resolution phase (virus already eliminated).
The novel `reverse phenotyping' approach used in this study could become a powerful tool for the identification of antigen-reactive T cell receptors. This is important for the rapid development of therapies and vaccines against emergent viruses such as SARS-CoV-2.
This work, initiated by Kilian Schober (TU Munich) and Herbert Schiller (ILBD/CPC-M, DZL site Munich), demonstrates once again how the rapid initiation of collaborations between multiple research institutions in this pandemic has led to new insights. Researchers from ILBD/CPC-M, ICB (both Helmholtz Zentrum München), TU München, LMU Klinikum, Asklepios Klinik München-Gauting and Uni Erlangen were involved in the work.