Vocanson Marc, Hennino Anca, Cluzel-Tailhardat Magalie, Saint-Mezard Pierre, Benetiere Josette, Chavagnac Cyril, Berard Frederic, Kaiserlian Dominique, Nicolas Jean-François
IFR 128 BioSciences Lyon-Gerland, Institut National de la Santé et de la Recherche Médicale U503, Lyon Cedex, France.
J Invest Dermatol. 2006 Apr;126(4):815-20. doi: 10.1038/sj.jid.5700174.
Allergic contact dermatitis (ACD) to strong experimental haptens is mediated by specific CD8+ T cells. Here, we show that similar mechanisms occur for weak haptens, which comprise the vast majority of chemicals responsible for human ACD. We used a model of ACD, that is, the contact hypersensitivity reaction, to test for the allergenicity of three weak haptens involved in fragrance allergy. ACD to weak haptens could not be induced in normal mice. In contrast, mice acutely depleted in CD4+ T cells developed a typical ACD reaction to the three weak fragrance allergens that peaked 24 hours after challenge. Priming of CD8+ T cells was observed in draining lymph nodes 5 days after sensitization and development of ACD was associated with the infiltration of activated CD8+ T cells in the challenged skin. CD8+ T cells were effectors of the ACD reaction as in vivo treatment with depleting anti-CD8 mAbs abrogated the ACD responses and as purified CD8+ T cells could adoptively transfer ACD to naive recipients. In conclusion, our data demonstrate a dominant role of CD8+ T cells as initiators of ACD to weak haptens, and suggest that CD8+ T cells may represent potential targets for preventing or treating ACD.
对强实验性半抗原的过敏性接触性皮炎（ACD）由特异性CD8⁺ T细胞介导。在此，我们表明类似机制也适用于弱半抗原，而弱半抗原构成了导致人类ACD的绝大多数化学物质。我们使用ACD模型，即接触性超敏反应，来测试三种与香料过敏有关的弱半抗原的致敏性。正常小鼠无法诱导出对弱半抗原的ACD。相反，CD4⁺ T细胞急性耗竭的小鼠对三种弱香料过敏原产生了典型的ACD反应，在激发后24小时达到峰值。致敏5天后在引流淋巴结中观察到CD8⁺ T细胞的致敏，并且ACD的发展与激发皮肤中活化CD8⁺ T细胞的浸润有关。CD8⁺ T细胞是ACD反应的效应细胞，因为用耗竭性抗CD8单克隆抗体进行体内治疗可消除ACD反应，并且纯化的CD8⁺ T细胞可以将ACD过继转移给未致敏的受体。总之，我们的数据证明了CD8⁺ T细胞作为弱半抗原所致ACD引发剂的主导作用，并表明CD8⁺ T细胞可能是预防或治疗ACD的潜在靶点。
