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树突状细胞暴露于参考变应原激活 T 细胞:评估化学品致敏潜能的有前途的模型。

Activation of T cells by dendritic cells exposed to a reference sensitizer: Towards a promising model to assess the allergenic potential of chemicals.

机构信息

Department of Toxicology and Biometrology, National Institute for Research and Safety (INRS), Vandœuvre-lès-Nancy cedex, France.

Faculté de Médecine, INGRES, EA 7298, Université de Lorraine, Vandœuvre-lès-Nancy, France.

出版信息

Contact Dermatitis. 2018 Aug;79(2):67-75. doi: 10.1111/cod.12991. Epub 2018 Apr 10.

DOI:10.1111/cod.12991
PMID:29635784
Abstract

BACKGROUND

Low molecular weight chemicals constitute one of the major causes of occupational allergies. European legislation on chemicals recommends limiting the use of in vivo models for assessing the sensitizing potential of chemicals, and encourages the development of integrated alternative methods. An in vitro mouse model of bone marrow-derived dendritic cells (BMDCs) that showed good accuracy (75%) and sensitivity (69%) has previously been developed to assess the sensitizing potential of chemicals.

OBJECTIVE

To assess the ability of BMDCs to activate T cells (TCs) in vitro.

METHODS

BMDCs pre-exposed to the reference sensitizer ammonium hexachloroplatinate (AHCP) were co-cultured with different subpopulations of TCs. TC activation was assessed by surface marker expression, proliferation, and cytokine release.

RESULTS

The results showed significant activation of TCs co-cultured with dendritic cells pre-exposed to AHCP as evaluated by CD124 expression, proliferation, and cytokine secretion. Moreover, the response of TCs appeared to be Th2-oriented. Naive TCs were shown to be involved in this response, and the removal of regulatory TCs did not improve the cell response.

CONCLUSIONS

The BMDCs used in this previously developed model appear to have the ability to activate TCs, confirming that the BMDC model represents a reliable assay for assessing the sensitizing potential of chemicals.

摘要

背景

低分子量化学物质是职业性过敏的主要原因之一。欧洲化学品法规建议限制使用体内模型来评估化学品的致敏潜力,并鼓励开发综合替代方法。先前已经开发了一种基于骨髓来源树突状细胞(BMDC)的体外小鼠模型,该模型具有良好的准确性(75%)和敏感性(69%),可用于评估化学品的致敏潜力。

目的

评估 BMDC 在体外激活 T 细胞(TCs)的能力。

方法

将参考致敏剂六氯合铂酸铵(AHCP)预先暴露于 BMDC 的情况下,与不同亚群的 TCs 共培养。通过表面标志物表达、增殖和细胞因子释放来评估 TC 的激活。

结果

结果表明,与预先暴露于 AHCP 的树突状细胞共培养的 TCs 表现出显著的激活,这可通过 CD124 表达、增殖和细胞因子分泌来评估。此外,TC 的反应似乎是 Th2 定向的。幼稚 TCs 参与了这种反应,而去除调节性 TCs 并不能改善细胞反应。

结论

先前开发的模型中使用的 BMDC 似乎具有激活 TCs 的能力,这证实了 BMDC 模型是评估化学品致敏潜力的可靠检测方法。

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