Abstract Formaldehyde (FA) is a ubiquitous environmental pollutant and a group 1 carcinogen. CD8+ T cells are specific tumor killers in the adaptive immune system. In this study, 2.0 mg/m3 respiratory FA exposure to male mice was found to selectively reduce mature CD8+ T cells in the spleen and the CD8 T cells in the thymus. In order to monitor the exposure of FA in vitro, a fluorescent FA donor was utilized in the treatment of murine thymocytes. Cytotoxicity induced by FA was found to be not selective at single positive stage. Significant inhibition of the runt-related transcription factor-3, the critical transcriptional factors for CD8 lineage commitment, was found in FA-treated double positive cells. ThPOK, the transcriptional factor for CD4 commitment, was stimulated by FA in double positive cells. Increased expression of special AT-rich sequence-binding protein-1 and decreased expression of B-cell lymphoma/leukemia 11B, which are the upstream regulators of ThPOK and the runt-related transcription factor-3, were also observed in FA-treated double positive cells. These results demonstrate that FA could selectively inhibit the development of CD8+ T cells via the alteration of transcriptional factor expressions of thymocytes at double positive stages, which would potentially interfere with the immune defense against cancers.

中文翻译：

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甲醛抑制小鼠T淋巴细胞的发育

摘要 甲醛 (FA) 是一种普遍存在的环境污染物和 1 类致癌物质。CD8+ T 细胞是适应性免疫系统中的特异性肿瘤杀手。在这项研究中，发现雄性小鼠呼吸 2.0 mg/m3 FA 暴露可选择性减少脾脏中的成熟 CD8+ T 细胞和胸腺中的 CD8 T 细胞。为了在体外监测 FA 的暴露, 在小鼠胸腺细胞的治疗中使用了荧光 FA 供体。发现 FA 诱导的细胞毒性在单一阳性阶段没有选择性。在 FA 处理的双阳性细胞中发现了对矮小相关转录因子 3（CD8 谱系定型的关键转录因子）的显着抑制。ThPOK 是 CD4 定型的转录因子，在双阳性细胞中受到 FA 的刺激。在 FA 处理的双胞胎中也观察到了特殊的富含 AT 的序列结合蛋白 1 的表达增加和 B 细胞淋巴瘤/白血病 11B 的表达降低，这些细胞是 ThPOK 和矮小相关转录因子 3 的上游调节因子。阳性细胞。这些结果表明，FA 可以通过改变双阳性阶段胸腺细胞转录因子的表达来选择性地抑制 CD8+T 细胞的发育，这可能会干扰对癌症的免疫防御。