Skin sensitisation: immunological mechanisms and novel approaches to predictive testing

In recent years, our understanding of the complex cell and molecular events that together orchestrate the induction of skin sensitisation and the elicitation of allergic contact dermatitis has increased significantly. A more detailed appreciation of the relevant immunobiological mechanisms has translated into new opportunities to consider alternative approaches to hazard evaluation. One method that is based on an integrated assessment of the induction phase of skin sensitisation is the murine local lymph node assay (LLNA), in which contact allergens are identified as a function of their ability to induce proliferative responses in skin-draining lymph nodes. The LLNA has proved to be a reliable method for hazard identification, and has more recently been deployed for determination of the relative skin sensitising potency of chemicals as a first step in the risk assessment process. The method has now been endorsed by the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) as a stand-alone method for skin sensitisation testing and, although it is not an in vitro method, was found by ICCVAM to confer important advantages with respect to the number of animals required for the purposes of sensitisation testing, and a reduction in the trauma to which animals are potentially subjected. Notwithstanding progress that has been made with the LLNA, there is considerable interest in the development of in vitro alternatives, acid activity is currently focused in three main areas: the derivation of structure-activity relationships, the ability of chemicals to induce changes in, or responses by, cultured dendritic cells, and the stimulation by chemical allergens of T lymphocyte activation in vitro. Progress in these areas is reviewed.