Wirsdörfer Florian, Cappuccini Federica, Niazman Muska, de Leve Simone, Westendorf Astrid M, Lüdemann Lutz, Stuschke Martin, Jendrossek Verena
Department of Molecular Cell Biology, Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Virchowstrasse 173, 45122, Essen, Germany.
Radiat Oncol. 2014 Apr 25;9:98. doi: 10.1186/1748-717X-9-98.
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).
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.
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.
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.
淋巴细胞浸润是放射性肺炎和肺纤维化的常见特征，但其在致病过程中的作用仍不清楚。在此，我们研究了胸部照射对T细胞亚群的影响，重点关注免疫抑制性调节性T细胞（Treg）。
C57BL/6野生型小鼠（WT）仅接受麻醉（假手术对照组，0 Gy）或接受单次全胸照射（15 Gy）。在照射后10至84天收集肺组织、脾脏和颈部淋巴结中的免疫细胞，并通过流式细胞术进行表型分析。
全胸照射在照射后42天和84天引起CD3+ T细胞流入增加。相比之下，局部照射导致外周淋巴组织中CD3+ T细胞持续减少。有趣的是，我们观察到在照射后第21天，表达转录因子叉头框P3（FoxP3）的CD4+ T细胞比例在局部和全身均显著增加，FoxP3是小鼠Treg的表型标志物。Treg的积累与表达具有募集和免疫抑制活性特征的表面蛋白的T细胞水平增加有关，例如CD103、CTLA-4和CD73。重要的是，此时分离的Treg能够与从对照小鼠分离的Treg一样有效地抑制CD4+效应T细胞。
适应性免疫系统对全胸照射的反应特征为局部免疫激活和全身免疫抑制。免疫抑制性CD4+ FoxP3+ Treg的短暂积累可能是保护肺免受过度炎症诱导的组织损伤所必需的。进一步的研究应确定Treg积累的潜在机制及其在放射性肺病发病机制中的作用。
