Thorax irradiation triggers a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells.
BACKGROUND
Lymphocyte infiltration is a common feature of radiation-induced pneumonitis and fibrosis, but their contribution to the pathogenic processes is still unclear. Here, we addressed the impact of thorax irradiation on the T 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 single dose of whole thorax irradiation (15 Gy). Immune cells from lung tissue, spleen, and cervical lymph nodes were collected 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. In contrast, 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 transcription factor forkhead box P3 (FoxP3), the phenotypic marker for murine Treg, at day 21 post-irradiation. The accumulation of Treg was associated with increased levels of T cells expressing surface proteins characteristic for recruitment and immunosuppressive activity, e.g. CD103, CTLA-4 and CD73. Importantly, Treg isolated at this time point were able to suppress 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 local immunoactivation and systemic immunosuppression. The transient accumulation of immunosuppressive CD4+ FoxP3+ Treg may be required to protect the lung against excessive inflammation-induced tissue damage. Further investigations shall define the mechanisms underlying the accumulation of Treg and their role for the pathogenesis of radiation-induced lung disease.
Florian
F
Wirsdörfer
Federica
F
Cappuccini
Muska
M
Niazman
Simone
S
de Leve
Astrid M
AM
Westendorf
Lutz
L
Lüdemann
Martin
M
Stuschke
Department of Molecular Cell Biology, Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Virchowstrasse 173, 45122, Essen, Germany. verena.jendrossek@uni-due.de.
Verena
V
Jendrossek
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013909:Thorax / Q000528:radiation effects*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse