Investigating the role of antigen-specific regulatory T cells in SARS-CoV-2 infection and immunization

Infection by SARS-CoV-2 results in COVID-19, a disease driven by immunopathology -- damaging inflammation to the infected individual caused by their own immune system. Conventional T-cells are cells that protect our body from pathogens by boosting inflammation and killing infected cells; they are crucial for protection in SARS-CoV-2 infection but can contribute to immunopathology in severe COVID-19. Regulatory T(REG)-cells are immunosuppressive cells that act on conventional T-cells to prevent out-of-control antiviral responses causing immunopathology. Conventional T-cells and TREG-cells function by specifically recognizing one single protein fragment, ie. a section of the SARS-CoV-2 virus, to identify infected target cells and harmful conventional T-cells respectively. The role of SARS-CoV-2-specific TREG-cells in SARS-CoV-2 infection and severe COVID-19 remains unknown. We hypothesize that the SARS-CoV-2-specific TREG-cells in severe COVID-19 are insufficiently curtailing the exaggerated inflammation due to dysfunctional suppressive activity. We are interested in identifying the magnitude of SARS-CoV-2-specific TREG-cell response (the number of responsive cells), the TREG phenotype (the subtype of TREG-cells responding) and their suppressive capacity (the ability of responsive TREG-cells to prevent the activity of conventional T-cells). We will investigate this response in a range of severities, from asymptomatic individuals to severe COVID-19 patients admitted to the ICU. Our characterization of TREG-cells will enable us to better understand the role of TREG-mediated immune regulation in severe COVID-19. By identifying efficiently suppressive TREG populations, our findings will contribute to the development of TREG-based therapies in pulmonary disease.