Rousset, F. Strategy for the Prediction of Skin Sensitisation:� An Alternative to Animal Testing.� ATLA 1999.� 27:� 116.

 

Contact hypersensitivity (CHS) is a form of T-cell-mediated delayed hypersensitivity following� an epicutaneous exposure to low molecular weight, highly reactive chemicals.� One of the challenges of alternatives to animal testing is to be able to propose a coherent strategy, based on detailed knowledge of this multistep and multifactorial immune reaction.� Research is focused on the sensitisation phase, because it is at this time-point that na�ve T lymphocytes are primed and differentiate into antigen-specific effector cells.� The last 4 years have been marked by two major breakthroughs that will permit, in the near future, the development of in vitro tests, predictive of the skin sensitisation potential of chemicals.� Firstly, it has been established that, contrary to the protein-mediated delayed type hypersensitivity which is a CD4-mediated immune reaction, CHS is CD8-mediated.� This implicates the development of in vitro tests, based on antigen-specific cytotoxicity.� Secondly, it is now possible to generate in vitro dendritic cells, the cells responsible for the link between skin and lymphoid organs.� Studies, based on morphology, phenotypic and functional evolution of these cells once they encounter chemicals in vitro, will permit the identification of mechanisms, or markers, specifically induced by sensitisers.� Finally, a strategy including the development of structure-activity models, metabolism studies, and an in vitro approach based on dendritic cell modifications, T-cell-dendritic cell interactions, and reconstructed skin models, will be presented.�