Thorax irradiation triggers a local and systemic accumulation of immunosuppressive CD4+ FoxP3+ regulatory T cells

Radiation Oncology

Verena Jendrossek³  Martin Stuschke²  Lutz Lüdemann²  Astrid M Westendorf¹  Simone de Leve³  Muska Niazman³  Federica Cappuccini³  Florian Wirsdörfer³ 

[1] Department of Infection Immunology, Institute of Microbiology, Medical Faculty, University of Duisburg-Essen, Essen, Germany;Department of Radiotherapy, Medical Faculty, University of Duisburg-Essen, Essen, Germany;Department of Molecular Cell Biology, Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Virchowstrasse 173, 45122, Essen, Germany

关键词: Fibrosis;    Pneumonitis;    T-lymphocytes;    Regulatory T cells;    Thorax irradiation;   

Others  :  805484
DOI  :  10.1186/1748-717X-9-98

 received in 2014-01-15, accepted in 2014-04-09,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Wirsdörfer et al.; licensee BioMed Central Ltd.

【 图 表 】

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