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. Na & iuml;ve 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 (T-RM) 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 T-RM in mice, but no decline in antigen-matched circulating memory T cells. Prolonged loss of lung T-RM 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 T-RM that was derived largely from circulating memory CD8(+) T cells. Designing effective vaccination strategies to regenerate T-RM will be important in combating the immunological effects of radiation exposure.