Differential immunotoxicity induced by two different windows of developmental trichloroethylene exposure.
Differential immunotoxicity induced by two different windows of developmental trichloroethylene exposure.
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DOI：
10.1155/2014/982073
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发表时间：
2014
影响因子：
4
通讯作者：
Blossom SJ
中科院分区：
文献类型：
--
作者：
Gilbert KM;Woodruff W;Blossom SJ
发育过程中接触环境毒物可能会引起免疫系统改变，从而导致成年期自身免疫性疾病。我们已经证明，MRL+/+ 小鼠从妊娠第 0 天（GD）到出生后第 49 天（PND）持续暴露于三氯乙烯（TCE）会改变 CD4+ T 细胞功能的几个方面。该暴露窗口对应于人类的受孕-青春期/青年期。更狭义地定义 TCE 发育暴露窗口会导致免疫毒性，从而建立避免和/或干预最有效的阶段。目前的研究将连续TCE暴露分为两个独立的窗口，即仅妊娠期（GD0至出生（PND0））和仅生命早期（PND0-PND49）。在 PND49 时检查小鼠 CD4+ T 细胞功能的特定变化。在两组发育暴露小鼠的外周 CD4+ T 细胞中发现了发育暴露的一种潜在长期影响，即反转录转座子表达的变化表明表观遗传改变。有趣的是，某些其他影响，例如胸腺细胞结构的改变，仅在妊娠期间暴露于 TCE 的小鼠中发现。相比之下，仅在生命早期暴露于 TCE 的小鼠中发现外周 CD4+ T 细胞的记忆/激活细胞亚群的扩张。不同的发育期 TCE 暴露时间可能会产生不同的功能后果。
Developmental exposure to environmental toxicants may induce immune system alterations that contribute to adult stage autoimmune disease. We have shown that continuous exposure of MRL+/+ mice to trichloroethylene (TCE) from gestational day (GD) 0 to postnatal day (PND) 49 alters several aspects of CD4+ T cell function. This window of exposure corresponds to conception-adolescence/young adulthood in humans. More narrowly defining the window of TCE developmental exposure causes immunotoxicity that would establish the stage at which avoidance and/or intervention would be most effective. The current study divided continuous TCE exposure into two separate windows, namely, gestation only (GD0 to birth (PND0)) and early-life only (PND0-PND49). The mice were examined for specific alterations in CD4+ T cell function at PND49. One potentially long-lasting effect of developmental exposure, alterations in retrotransposon expression indicative of epigenetic alterations, was found in peripheral CD4+ T cells from both sets of developmentally exposed mice. Interestingly, certain other effects, such as alterations in thymus cellularity, were only found in mice exposed to TCE during gestation. In contrast, expansion of memory/activation cell subset of peripheral CD4+ T cells were only found in mice exposed to TCE during early life. Different windows of developmental TCE exposure can have different functional consequences.