Department of Hygiene, Kawasaki Medical School, Kurashiki, 701-0192, Japan.
Department of Biofunctional Chemistry, Graduate School of Environmental and Life Science, Okayama University, Okayama, 700-8530, Japan.
Environ Health Prev Med. 2020 Oct 8;25(1):59. doi: 10.1186/s12199-020-00900-6.
Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8 T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8 T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8 lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8 lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8 T cells, cultured human CD8 T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8 lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.
石棉暴露已知会导致恶性间皮瘤，这与预后不良有关。我们专注于研究并检查了石棉暴露对细胞毒性 T 淋巴细胞（CTL）的分化和功能的影响。CTL 能够在抗原刺激后从幼稚 CD8 T 细胞分化后特异性攻击肿瘤细胞。暴露于温石棉 B 会抑制混合淋巴细胞反应（MLR）中 CTL 的分化，并与 CD8 T 细胞增殖减少有关。此外，为了研究暴露于石棉后与抑制 CTL 分化相关的机制，我们专注于细胞因子白细胞介素 2（IL-2），它参与 T 细胞增殖。我们的研究结果表明，尽管可能改善抑制的 CTL 功能，但 IL-2 水平不足不是石棉暴露抑制 CTL 诱导的主要原因。此外，还研究了来自胸膜斑块（PP）和恶性间皮瘤（MM）患者的暴露于石棉的个体的外周血 CD8 淋巴细胞的功能特性。与 PP 阳性个体相比，刺激后 MM 患者的 CD8 淋巴细胞中的穿孔素水平较低。与健康志愿者或 PP 阳性个体相比，MM 组 IFN-γ 的产生能力趋于降低。为了确定慢性和直接的石棉暴露是否影响 CD8 T 细胞的功能，采用体外培养的人 CD8 T 细胞作为体外模型，并对其进行长期温石棉（CH）暴露。这导致细胞内穿孔素和分泌的 IFN-γ水平降低。这些发现表明，CD8 淋巴细胞功能受损可能是由于石棉暴露引起的，这未能抑制 MM 的发展。因此，我们的研究揭示了石棉暴露对 CTL 的新影响，这可能有助于制定和实施预防和治疗恶性间皮瘤的有效策略。
