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 naïve 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.