Regenerating murine CD8+ lung tissue resident memory T cells after targeted radiation exposure

Mariah Hassert; Lecia L Pewe; Rui He; Mohammad Heidarian; Pornpoj Phruttiwanichakun; Stephanie van de Wall; Madison R Mix; Aliasger K Salem; Vladimir P Badovinac; John T Harty

doi:10.1084/jem.20231144

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Regenerating murine CD8+ lung tissue resident memory T cells after targeted radiation exposure

Journal article

Open access

Peer reviewed

Regenerating murine CD8+ lung tissue resident memory T cells after targeted radiation exposure

Mariah Hassert, Lecia L Pewe, Rui He, Mohammad Heidarian, Pornpoj Phruttiwanichakun, Stephanie van de Wall, Madison R Mix, Aliasger K Salem, Vladimir P Badovinac and John T Harty

The Journal of experimental medicine, Vol.221(3), e20231144

03/04/2024

DOI: 10.1084/jem.20231144

PMCID: PMC10873130

PMID: 38363548

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Abstract

Radiation exposure occurs during medical procedures, nuclear accidents, or spaceflight, making effective medical countermeasures a public health priority. Naïve T cells are highly sensitive to radiation-induced depletion, although their numbers recover with time. Circulating memory CD8+ T cells are also depleted by radiation; however, their numbers do not recover. Critically, the impact of radiation exposure on tissue-resident memory T cells (TRM) remains unknown. Here, we found that sublethal thorax-targeted radiation resulted in the rapid and prolonged numerical decline of influenza A virus (IAV)-specific lung TRM in mice, but no decline in antigen-matched circulating memory T cells. Prolonged loss of lung TRM was associated with decreased heterosubtypic immunity. Importantly, boosting with IAV-epitope expressing pathogens that replicate in the lungs or peripheral tissues or with a peripherally administered mRNA vaccine regenerated lung TRM that was derived largely from circulating memory CD8+ T cells. Designing effective vaccination strategies to regenerate TRM will be important in combating the immunological effects of radiation exposure.

Details

Title: Subtitle: Regenerating murine CD8+ lung tissue resident memory T cells after targeted radiation exposure
Creators: Mariah Hassert - University of Iowa
Lecia L Pewe - University of Iowa
Rui He - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA
Mohammad Heidarian - University of Iowa
Pornpoj Phruttiwanichakun - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA
Stephanie van de Wall - University of Iowa
Madison R Mix - University of Iowa
Aliasger K Salem - University of Iowa
Vladimir P Badovinac - Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
John T Harty - Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.221(3), e20231144
DOI: 10.1084/jem.20231144
PMID: 38363548
PMCID: PMC10873130
NLM abbreviation: J Exp Med
eISSN: 1540-9538
Grant note: P30CA086862 / NIH HHS NCI NIH HHS
Language: English
Date published: 03/04/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984559878402771

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