Kimber I, Pichowski J S, Basketter D A, Dearman R J
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK.
Toxicol Lett. 1999 Jun 1;106(2-3):237-46. doi: 10.1016/s0378-4274(99)00069-7.
Progress in our understanding of the immunobiological mechanisms that cause skin sensitization and allergic contact dermatitis has facilitated consideration of alternative approaches to hazard evaluation. One such is the murine local lymph node assay in which, in contrast to more traditional guinea pig tests, sensitizing activity is measured as a function of events associated with the induction, rather than the elicitation, phase of contact hypersensitivity. Activity in the local lymph node assay is dependent upon all of those immunological events that are initiated following first encounter with chemical allergen and which result in the stimulation of T lymphocyte proliferative responses in lymph nodes draining the site of exposure. In this respect the assay embraces in an holistic way the induction of skin sensitization. With the objective of developing in vitro approaches to hazard identification, consideration has been given to discrete immunological responses that characterize the induction of skin sensitization. Most attention has focused upon the changes induced by chemical allergens in the phenotype and function of epidermal Langerhans cells and in cytokine expression. In addition, attempts have been made to identify contact allergens as a function of their ability to provoke in vitro specific responses by unprimed T lymphocytes. These novel approaches to skin sensitization testing and their potential utility in the context of toxicological evaluations are reviewed in this article.
我们对引起皮肤致敏和过敏性接触性皮炎的免疫生物学机制的理解取得了进展，这促进了对危害评估替代方法的思考。其中一种方法是小鼠局部淋巴结试验，与更传统的豚鼠试验不同，该试验中致敏活性是根据与接触性超敏反应诱导期而非激发期相关的事件来衡量的。局部淋巴结试验中的活性取决于首次接触化学过敏原后引发的所有免疫事件，这些事件会导致暴露部位引流淋巴结中的T淋巴细胞增殖反应受到刺激。在这方面，该试验以整体方式涵盖了皮肤致敏的诱导过程。为了开发体外危害识别方法，人们已考虑了表征皮肤致敏诱导过程的离散免疫反应。大部分注意力集中在化学过敏原引起的表皮朗格汉斯细胞表型和功能以及细胞因子表达的变化上。此外，人们还尝试根据接触性过敏原激发未致敏T淋巴细胞体外特异性反应的能力来识别它们。本文将对这些皮肤致敏测试的新方法及其在毒理学评估中的潜在用途进行综述。
