Lung-resident SARS-CoV-2 peptide-specific immune responses in perfused 3D human lung explant models

Multi-specific and long-lasting T-cell immunity has been recognized to indicate long-term protection against pathogens, including the novel coronavirus, SARS-CoV-2, which is the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovered from COVID-19 (COVID-19⁺) is beginning to be appreciated; however, the role of lung tissue-resident memory (lung TRM) T cells in SARS-CoV-2 infection is still being investigated. This is, in part, due to the lack of preclinical tissue models available to follow the convalescence period.

Here, we utilize a perfused three-dimensional (3D) human lung-tissue model and show pre-existing local T-cell immunity against SARS-CoV-2 proteins in lung tissues.

We report ex vivo maintenance of functional multi-specific IFN-γ-secreting lung TRM T cells in COVID-19⁺ and their induction in lung tissues of vaccinated COVID-19⁺ subjects. Importantly, we identify SARS-CoV-2 peptide-responding memory B cells and IgA⁺ plasma cells in ex vivo cultured lung tissues of COVID-19⁺. Furthermore, lung tissue IgA levels were increased in COVID-19⁺ and responded to peptide stimulation.

In our study, we highlight the importance of utilization of human lung-tissue models to understand the local antiviral immune response in the lung to protect against SARS-CoV-2 infection.