Immune responses to contact allergens: novel approaches to hazard evaluation

Progress in our understanding of the immunobiological mechanisms that cause skin sensitization and allergic contact dermatitis has facilitated conside ration of alternative approaches to hazard evaluation. One such is the muri ne local lymph node assay in which, in contrast to more traditional guinea pig tests, sensitizing activity is measured as a function of events associa ted with the induction, rather than the elicitation, phase of contact hyper sensitivity. Activity in the local lymph node assay is dependent upon all o f those immunological events that are initiated following first encounter w ith chemical allergen and which result in the stimulation of T lymphocyte p roliferative responses in lymph nodes draining the site of exposure. In thi s respect the assay embraces in an holistic way the induction of skin sensi tization. With the objective of developing in vitro approaches to hazard id entification, consideration has been given to discrete immunological respon ses that characterize the induction of skin sensitization. Most attention h as focused upon the changes induced by chemical allergens in the phenotype and function of epidermal Langerhans cells and in cytokine expression. In a ddition, attempts have been made to identify contact allergens as a functio n of their ability to provoke in vitro specific responses by unprimed T lym phocytes. These novel approaches to skin sensitization testing and their po tential utility in the context of toxicological evaluations are reviewed in this article. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.