Background: Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but theircontribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on theT cell compartment with a focus on immunosuppressive regulatory T cells (Treg).

Methods: C57BL/6 wild type mice (WT) received anesthesia only (sham controls, 0 Gy) or were exposed to a singledose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes werecollected 10 to 84 days post-irradiation and phenotypically characterized by flow cytometry.

Results: Whole thorax irradiation provoked an increased influx of CD3+ T cells at 42 and 84 days post-irradiation. Incontrast, local irradiation caused a sustained reduction in CD3+ T cells in peripheral lymphoid tissues. Interestingly,we observed a significant local and systemic increase in the fraction of CD4+ T cells expressing the transcriptionfactor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulationof Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment andimmunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able tosuppress CD4+ effector T cells to a similar extent as Treg isolated from control mice.

Conclusions: The response of the adaptive immune system to whole thorax irradiation is characterized by localimmunoactivation and systemic immunosuppression. The transient accumulation of immunosuppressive CD4+FoxP3+ Treg may be required to protect the lung against excessive inflammation-induced tissue damage. Furtherinvestigations shall define the mechanisms underlying the accumulation of Treg and their role for the pathogenesisof radiation-induced lung disease.