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 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.
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK. ian.kimber@ctl.zeneca.com
I
I
Kimber
J S
JS
Pichowski
D A
DA
Basketter
R J
RJ
Dearman
D000485:Allergens / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004817:Epidermis / Q000276:immunology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens