Radiation Induces Persistent Dysregulation and Functional Impairment in CD8+ T Cell Immunity

In addition to immediate cell lethality, radiation exposure has long-term effects on the immune system, particularly T lymphocytes, causing persistent functional abnormalities post-exposure. Uncertainties remain regarding the long-lasting consequences on T cell immunity in survivors of the acute radiation syndrome and the underlying mechanisms of those consequences. Here, we investigated delayed effects of acute radiation exposure on CD8+ T cell immunity using the Listeria monocytogenes infection model. Impaired CD8+ T cell activation, reduced terminal effector formation upon infection, and exacerbated listeriosis were found in mice at 4 weeks postirradiation with sublethal doses. To elucidate how radiation affects the functionality of CD8+ T cells at various differentiation stages, we performed single-cell transcriptomic profiling. Radiation altered cluster distribution pre-infection and impaired terminal effector and memory precursor effector formation post-infection. Differential gene analysis highlighted radiation-induced gene expression changes, including cytokines and mitochondrial proteins, in a cluster-specific manner post-infection. The study demonstrates dysfunction of newly replenished naïve T cells, which results in impaired CD8+ T cell immunity after irradiation.