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

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.

 
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NSF-PAR ID:
10491087
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ;
Publisher / Repository:
DOI PREFIX: 10.1084
Date Published:
Journal Name:
Journal of Experimental Medicine
Volume:
221
Issue:
3
ISSN:
0022-1007
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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    Basic Protocol 1: Isolation of bone marrow progenitor cells

    Basic Protocol 2: In vitro differentiation of dendritic cells with GM‐CSF

    Support Protocol 1: Preparation of conditioned medium from GM‐CSF producing J558L cells

    Basic Protocol 3: In vitro differentiation of dendritic cells with Flt3L

    Support Protocol 2: Preparation of Flt3L containing medium from B16‐Flt3L cells

    Basic Protocol 4: Expansion of cDC1s in vivo for use in ex vivo experiments

    Basic Protocol 5: Characterizing resting and activated dendritic cells

    Basic Protocol 6: Dendritic cell stimulation, antigenic cargo, and fixation

    Support Protocol 3: Preparation of model antigen coated microbeads

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    Support Protocol 5: Preparation of recombinant bacteria

    Basic Protocol 7: Immunocytochemistry immunofluorescence (ICC/IF)

    Support Protocol 6: Preparation of Alcian blue‐coated coverslips

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