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

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

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...

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Main Authors: Kayla F. Goliwas, Anthony M. Wood, Christopher S. Simmons, Rabisa Khan, Saad A. Khan, Yong Wang, Rekha Ramachandran, Joel L. Berry, Mohammad Athar, James A. Mobley, Young-il Kim, Victor J. Thannickal, Kevin S. Harrod, James M. Donahue, Jessy S. Deshane
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Bioengineering and Biotechnology
Subjects:
human lung-tissue model
SARS-CoV-2 infection
COVID-19
perfused lung explant
local antiviral immune response
Online Access:https://www.frontiersin.org/articles/10.3389/fbioe.2025.1587080/full
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Summary: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.
ISSN:2296-4185

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