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。 一些环境化学物质的表皮应用导致T细胞介导的炎症反应，称为变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集中在反应的诱导阶段。 关于过敏性接触性皮炎诱发的细胞和分子要求，人们知之甚少。 在这个建议中，我们假设：抗原呈递细胞和共刺激分子，他们表达的诱导和引发的CHS反应的要求是不同的。 我们将在小鼠中通过评估可以作为抗原呈递细胞引发反应的细胞类型来研究这个问题。 将检查已知对诱导过敏性接触性皮炎重要的MHC I类和II类抗原在应答激发期的作用。 基于我们的初步数据表明，半抗原引发的T细胞转移到ICAM-1缺陷小鼠引起降低CHS反应和半抗原引发的T细胞在小鼠中的发育受损，ICAM-1在CHS的诱发中的作用将被确定。 我们还将评估那些不能引起CHS的抗原呈递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，CHS在γ δ T细胞缺陷小鼠中显著增加，因此还将评估γ δ T细胞的潜在调节作用。 在基本水平上，这些结果将提供有关过敏性接触性皮炎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.