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Ionizing radiation induces lasting changes to the tissue resident memory T cell compartment
Abstract   Peer reviewed

Ionizing radiation induces lasting changes to the tissue resident memory T cell compartment

Mariah Hassert, Mohammad Heidarian, Vladimir P Badovinac and John T Harty
The Journal of immunology (1950), Vol.210(1_Supplement), p.156.10
05/01/2023
DOI: 10.4049/jimmunol.210.Supp.156.10

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Abstract

Abstract Exposure to sublethal ionizing radiation can occur through various mechanisms, including purposeful medical exposure, nuclear accidents, and acts of nuclear terrorism, making the development of effective medical countermeasures a high public health priority. The induction of DNA damage through reactive oxygen species makes rapidly dividing cells, such as naïve T cells highly sensitive to radiation induced depletion. A previous study demonstrated that broadly, circulating memory T cells are more resistant to numerical loss following radiation exposure compared to naïve T cells. However, the effects of radiation on the more recently described memory T cell subset, tissue resident memory T cells (T RM) remain unknown. T RMhave been identified as a critical T cell subset in protection from a number of infections including influenza, respiratory syncytial virus and malaria. In particular, lung T RMare critical for strain-transcending heterosubtypic immunity to influenza virus. In a murine model of influenza infection (IAV), we have found that sublethal thorax targeted radiation resulted in the rapid numerical decline of lung T RMwithout major alterations in circulating IAV-specific memory CD8+ T cells. The depletion of anti-IAV lung T RMwas long-lasting, and resulted in the loss of heterosubtypic immunity to IAV. Interestingly, any surviving T RMdisplay elevated granzyme B expression, indicating functional consequences for T RMfollowing radiation exposure, which could have implications for immune-mediated pathology. Designing effective vaccination strategies to reinvigorate this critical T cell subset will be an important step in combating the immunological effects of radiation exposure. 1F32AI174382-01

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