Contact sensitizers specifically increase MHC class II expression on murine immature dendritic cells.

C Herouet, M Cottin, J LeClaire, A Enk, F Rousset
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引用次数: 18

Abstract

Contact sensitivity is a T-cell-mediated immune disease that can occur when low-molecular-weight chemicals penetrate the skin. In vivo topical application of chemical sensitizers results in morphological modification of Langerhans cells (LC). Moreover, within 18 h, LC increase their major histocompatibility complex (MHC) class II antigens expression and migrate to lymph nodes where they present the sensitizer to T lymphocytes. We wanted to determine if such an effect could also be observed in vitro. However, because of the high genetic diversity encountered in humans, assays were performed with dendritic cells (DC) obtained from a Balb/c mouse strain. The capacity of a strong sensitizer, DNBS (2,4-dinitrobenzene sulfonic acid), to modulate the phenotype of bone marrow-derived DC in vitro, was investigated. A specific and marked increase of MHC class II molecules expression was observed within 18 h. To eliminate the use of animals in sensitization studies, the XS52 DC line was tested at an immature stage. A 30-min contact with the strong sensitizers DNBS and oxazolone, or the moderate mercaptobenzothiazole, resulted in upregulation of MHC class II molecules expression, analyzed after 18-h incubation. This effect was not observed with irritants (dimethyl sulfoxide and sodium lauryl sulfate) nor with a neutral molecule (sodium chloride). These data suggested the possibility of developing an in vitro model for the identification of the sensitizing potential of chemicals, using a constant and non animal-consuming material.

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接触致敏剂特异性增加小鼠未成熟树突状细胞MHC II类表达。
接触敏感性是一种t细胞介导的免疫疾病,当低分子化学物质穿透皮肤时就会发生。在体内局部应用化学增敏剂导致朗格汉斯细胞(LC)的形态改变。此外,在18小时内,LC增加了其主要组织相容性复合体(MHC) II类抗原的表达,并迁移到淋巴结,在那里它们对T淋巴细胞呈敏化剂。我们想确定这种效应是否也能在体外观察到。然而,由于在人类中遇到的高度遗传多样性,因此使用从Balb/c小鼠品系获得的树突状细胞(DC)进行了检测。研究了强增敏剂DNBS(2,4-二硝基苯磺酸)在体外调节骨髓源性DC表型的能力。在18小时内观察到MHC II类分子表达特异性显著增加。为了消除致敏研究中使用动物,在未成熟阶段对XS52 DC系进行了测试。与强致敏剂DNBS和恶唑酮或中度巯基苯并噻唑接触30分钟,可导致MHC II类分子表达上调,孵育18小时后分析。这种效果在刺激物(二甲亚砜和十二烷基硫酸钠)和中性分子(氯化钠)中没有观察到。这些数据表明,有可能开发一种体外模型,用于鉴定化学物质的致敏潜力,使用恒定和非动物消耗的材料。
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