AUTHOR=Goliwas Kayla F. , Wood Anthony M. , Simmons Christopher S. , Khan Rabisa , Khan Saad A. , Wang Yong , Ramachandran Rekha , Berry Joel L. , Athar Mohammad , Mobley James A. , Kim Young-il , Thannickal Victor J. , Harrod Kevin S. , Donahue James M. , Deshane Jessy S. 

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

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2025.1587080

DOI=10.3389/fbioe.2025.1587080

ISSN=2296-4185

ABSTRACT=IntroductionMulti-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.MethodsHere, 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.ResultsWe 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.DiscussionIn 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.