ALLERGIC CONTACT DERMATITIS--MECHANISMS OF ELICITATION

皮肤是保护其他器官和内部组织免受外部环境影响的主要屏障。皮肤表面应用一些环境化学物质会导致T细胞介导的炎症反应，称为变态反应性接触性皮炎或接触性超敏反应(CHS)。大多数研究过敏性接触性皮炎的免疫发病机制的研究都集中在反应的诱导阶段。对于过敏性接触性皮炎的细胞和分子需求，我们知之甚少。在这个方案中，我们假设：抗原提呈细胞及其表达的共刺激分子对CHS反应的诱导和诱导是不同的。我们将通过评估可以作为抗原提呈细胞来激发反应的细胞类型，在小鼠身上研究这一问题。已知对诱发变态反应性接触性皮炎很重要的MHC I类和II类抗原将在反应的激发阶段进行检查。根据我们的初步数据表明，将半抗原免疫的T细胞转移到ICAM-1缺陷小鼠引起的CHS反应降低，半抗原免疫的T细胞的发育受到损害，ICAM-1在CHS诱导中的作用将被确定。我们还将评估那些不能诱导CHS的抗原提呈细胞是否有能力使已经对半抗原致敏的动物脱敏。由于我们目前的结果表明，在GammadeltaT细胞缺陷小鼠中，CHS显著增加，因此也将评估GammadeltaT细胞的潜在调节作用。在基础水平上，这些结果将提供关于过敏性接触性皮炎的发病机制以及皮肤和免疫系统之间相互作用的新信息。在临床层面上，这些信息应该有助于制定预防和治疗这种常见皮肤病的新的具体策略。

The skin is the primary barrier protecting other organs and internal tissues from the external environment. Epicutaneous application of some environmental chemicals results in a T cell- mediated inflammatory response termed allergic contact dermatitis or contact hypersensitivity (CHS). Most studies examining the immmunpathogenesis of allergic contact dermatitis have focused on the induction phase of the response. Much less is known about the cellular and molecular requirements for elicitation of allergic contact dermatitis once sensitization has occurred. In this proposal, we hypothesize that: the requirement of antigen presenting cells and the costimulatory molecules that they express for induction and elicitation of CHS reactions are different. We will examine this issue in mice by assessing the types of cells that can serve as antigen presenting cells for elicitation of the response. MHC class I and class II antigens that are known to be important for induction of allergic contact dermatitis will be examined for their role during the elicitation phase of the response. Based on our preliminary data indicating that transfer of hapten primed T cells to ICAM-1 deficient mice elicited a reduced CHS response and the development of hapten primed T cells in the mice was impaired, the role of ICAM-1 in the elicitation of CHS will be determined. We will also evaluate whether those antigen-presenting cells that are unable to elicit CHS have the capacity to desensitize animals that have already been sensitized to hapten. Because our current results indicate that CHS is significantly increased in gammadeltaT cell deficient mice, the potential regulatory effects of gammadeltaT cells will also be evaluated. On a basic level, the results will provide new information concerning the pathogenesis of allergic contact dermatitis and interactions between the skin and the immune system. On a clinical level, the information should be useful for the development of new specific strategies for the prevention and treatment of this common skin disease.