Whole-body irradiation leads to long-term impairment in the maintenance and function of self- and non-self-epitope specific naïve CD4 T cells 3266

Abstract Description Increasing demand for nuclear power and radiotherapy has expanded new avenues for whole-body irradiation (WBI) to humans, urging the need to understand its impact on immune cells. While existing studies primarily focus on the numerical recovery of naïve T cells post-WBI, impact of WBI on naïve T cell function is less explored. Here, we used Experimental Autoimmune Encephalomyelitis (EAE) and LCMV-Arm infection models in mice to test naïve CD4 T cell function post-WBI. Mice subjected to sub-lethal WBI sustain lymphopenia after 10 days, and achieves lymphoreplete state by 40 days post WBI. Infection or immunization of lymphopenic WBI survivors led to poor protective (GP66) or pathogenic (MOG38) CD4 effector response respectively, suggesting CD4 T cell intrinsic damage by WBI. Interestingly, MOG immunization of lymphoreplete WBI survivors +/- pertussis toxin potentiated EAE disease, suggestive of WBI mediated Blood-brain barrier (BBB) impairment as a major T cell extrinsic factor contributing to this phenotype. In the infection model, this WBI mediated BBB impairment also led to an increase in total CD4 TRM, and GP66-specific CD4 T cells in the brain of mice. Overall, WBI directly impacts the number and function of both auto-reactive and virus-specific CD4 T cells, while helping them enter the BBB by changing the environment. This study is a step towards understanding the timing for medical interventions like vaccination strategies to improve T cell function in WBI survivors. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)