ALLERGIC CONTACT DERMATITIS--MECHANISMS OF ELICITATION

皮肤是保护其他器官和内部组织免受外界环境侵害的主要屏障。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，称为过敏性接触性皮炎或接触性超敏反应（CHS）。大多数关于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。很少知道细胞和分子的要求引发过敏性接触性皮炎一旦发生致敏。在本提案中，我们假设：抗原提呈细胞及其表达的共刺激分子诱导和激发CHS反应的需求是不同的。我们将通过评估可以作为抗原提呈细胞引发反应的细胞类型，在小鼠中研究这个问题。已知对诱发过敏性接触性皮炎很重要的MHC I类和II类抗原将被检查其在反应引发阶段的作用。我们的初步数据表明，将半抗原引发的T细胞转移到缺乏ICAM-1的小鼠身上，会导致CHS反应减弱，并且半抗原引发的T细胞在小鼠体内的发育受损，因此我们将确定ICAM-1在引发CHS中的作用。我们还将评估那些不能引发CHS的抗原呈递细胞是否有能力使已经对半抗原敏感的动物脱敏。由于我们目前的结果表明，CHS在gammadeltaT细胞缺陷小鼠中显著增加，因此我们还将评估gammadeltaT细胞的潜在调节作用。在基本层面上，这些结果将为过敏性接触性皮炎的发病机制以及皮肤与免疫系统之间的相互作用提供新的信息。在临床层面，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战略。

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.