Sequential radiation exposure: uncovering the potential of low dose ionizing radiation in mitigating high dose effects on immune cells.

ABSTRACT

PURPOSE: The radioadaptive response refers to a phenomenon wherein exposure to a low dose of ionizing radiation (LDIR) can induce a protective response in cells or organisms, reducing the adverse effects of a subsequent higher dose of ionizing radiation (HDIR). However, it is possible to administer the low dose after the challenge dose. This study was conducted to determine the potential mitigating effect of LDIR administered after HDIR on mice immune cells. MATERIALS AND METHODS: Alongside the conventional adaptive response setting, one group of mice was initially exposed to HDIR and subsequently treated with LDIR. Neutrophil activation was done using DHR-reducing assay and cell proliferation was evaluated through CFSE-dilution assay in helper (CD4+) and cytotoxic (CD8+) T cells. Cytokine production by these T cell subsets was also assessed by intracellular staining using flow cytometry. RESULTS: The results of this study revealed no change in neutrophil function between any of the mice groups compared to the untreated control group. Although significant changes were not detected in the proliferation of CD4+ T cells, decreased proliferation was observed in stimulated CD8+ T cells in the HDIR group. In contrast to IFN-É£, which showed no evident change in either of the T cell subsets after stimulation, IL-4 was rigorously dropped in stimulated CD4+ T cells in the HDIR group. CONCLUSIONS: In summary, the results of this study indicated that the administration of LDIR to mice before HDIR was not able to reduce the detrimental effects of HDIR in our experimental setting. Instead, we observed a mitigating effect of LDIR when administered after the challenge dose. This suggests that not only the dose and duration but also the order of LDIR relative to HDIR affects its efficacy.