Vocanson Marc, Hennino Anca, Rozières Aurore, Cluzel-Tailhardat Magalie, Poyet Gaelle, Valeyrie Magalie, Bénetière Josette, Tédone Rosine, Kaiserlian Dominique, Nicolas Jean-François
Faculté de Médecine, Université Lyon1, Lyon-Sud, France.
J Invest Dermatol. 2009 May;129(5):1185-91. doi: 10.1038/jid.2008.352. Epub 2008 Nov 13.
Allergic contact dermatitis (ACD) is mediated by hapten-specific CD8+ T cells and downregulated by CD4+ T cells. We have recently shown in a model of ACD to weak haptens that priming of IFNgamma-producing CD8+ T cells and the development of skin inflammation could be obtained in mice deficient in CD4+ T cells. Here we show that IFNgamma production by lymph node (LN) cells draining the site of skin sensitization of CD4+ T-cell-deficient mice is a marker of the sensitizing properties of weak haptens. LN cells from mice sensitized as in the classical local lymph node assay (LLNA) were recovered at day 5, then cultured for 20 hours in the presence of submitogenic doses of phytohemagglutinin, and finally tested for the production of IFNgamma. Results show that: (i) production of INFgamma by LN cells was induced by weak and moderate allergens in a dose-dependent fashion; (ii) the magnitude of IFNgamma production paralleled the sensitizing properties of allergens allowing to classify them as moderate or weak haptens; (iii) chemicals without sensitizing properties were unable to stimulate IFNgamma production by LN cells. Therefore, the IFNgamma LLNA appears as a sensitive, specific, and robust assay to detect weak contact allergens.
过敏性接触性皮炎(ACD)由半抗原特异性CD8 + T细胞介导,并受到CD4 + T细胞的下调。我们最近在对弱半抗原的ACD模型中表明,在缺乏CD4 + T细胞的小鼠中可以诱导产生IFNγ的CD8 + T细胞启动并引发皮肤炎症。在此我们表明,来自CD4 + T细胞缺陷小鼠皮肤致敏部位引流淋巴结(LN)细胞产生的IFNγ是弱半抗原致敏特性的标志物。在第5天回收来自如经典局部淋巴结试验(LLNA)中致敏小鼠的LN细胞,然后在亚致有丝分裂剂量的植物血凝素存在下培养20小时,最后检测IFNγ的产生。结果表明:(i)LN细胞产生IFNγ由弱和中度变应原以剂量依赖性方式诱导;(ii)IFNγ产生的程度与变应原的致敏特性平行,从而能够将它们分类为中度或弱半抗原;(iii)无致敏特性的化学物质不能刺激LN细胞产生IFNγ。因此,IFNγ-LLNA似乎是一种检测弱接触性变应原的灵敏、特异且可靠的试验。