Diesel exhaust particles (DEP) are major constituents of ambient air pollution and their adverse health effect is an area of intensive investigations. With respect to the immune system, DEP have attracted significant research attention as a factor that could influence allergic diseases interfering with cytokine production and chemokine expression. With this exception, scant data are available on the impact of DEP on lymphocyte homeostasis. Here, the effects of nanoparticles from Euro 4 (E4) and Euro 5 (E5) light duty diesel engines on the phenotype and function of T lymphocytes from healthy donors were evaluated. T lymphocytes were isolated from peripheral blood obtained from healthy volunteers and subsequently stimulated with different concentration (from 0.15 to 60 μg/ml) and at different time points (from 24 h to 9 days) of either E4 or E5 particles. Immunological parameters, including apoptosis, autophagy, proliferation levels, mitochondrial function, expression of activation markers and cytokine production were evaluated by cellular and molecular analyses. DEP exposure caused a pronounced autophagic-lysosomal blockade, thus interfering with a key mechanism involved in the maintaining of T cell homeostasis. Moreover, DEP decreased mitochondrial membrane potential but, unexpectedly, this effect did not result in changes of the apoptosis and/or necrosis levels, as well as of intracellular content of adenosine triphosphate (ATP). Finally, a down-regulation of the expression of the alpha chain of the interleukin (IL)-2 receptor (i.e., the CD25 molecule) as well as an abnormal Th1 cytokine expression profile (i.e., a decrease of IL-2 and interferon (IFN)-γ production) were observed after DEP exposure. No differences between the two compounds were detected in all studied parameters. Overall, our data identify functional and phenotypic T lymphocyte parameters as relevant targets for DEP cytotoxicity, whose impairment could be detrimental, at least in the long run, for human health, favouring the development or the progression of diseases such as autoimmunity and cancer.

中文翻译：

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体外柴油机排气颗粒暴露会影响T淋巴细胞的表型和功能。

柴油机废气颗粒（DEP）是环境空气污染的主要成分，其不良健康影响是深入研究的领域。关于免疫系统，DEP作为可能影响会干扰细胞因子产生和趋化因子表达的变应性疾病的因素而引起了广泛的研究关注。除此例外，尚缺乏DEP对淋巴细胞稳态影响的数据。在这里，评估了来自欧洲4（E4）和欧洲5（E5）轻型柴油机的纳米颗粒对健康供体T淋巴细胞表型和功能的影响。从健康志愿者的外周血中分离出T淋巴细胞，然后以不同的浓度（从0开始刺激）。15至60μg/ ml）和E4或E5颗粒的不同时间点（24小时至9天）。通过细胞和分子分析来评估免疫学参数，包括细胞凋亡，自噬，增殖水平，线粒体功能，激活标志物的表达和细胞因子的产生。DEP暴露引起明显的自噬-溶酶体阻滞，从而干扰了维持T细胞稳态的关键机制。此外，DEP降低了线粒体膜电位，但出乎意料的是，这种作用并未导致细胞凋亡和/或坏死水平以及三磷酸腺苷（ATP）细胞内含量的变化。最后，白介素（IL）-2受体的α链表达下调（即，DEP暴露后，观察到CD25分子）以及异常的Th1细胞因子表达谱（即IL-2和干扰素（IFN）-γ产生减少）。在所有研究参数中均未检测到两种化合物之间的差异。总体而言，我们的数据将功能性和表型T淋巴细胞参数确定为DEP细胞毒性的相关靶标，DEP细胞毒性的损害至少从长期来看可能对人体健康有害，有利于自身免疫性疾病和癌症等疾病的发生或发展。