Cutaneous antigen presenting cells (APC) play a critical role in the initiation of T-cell mediated immune responses in the skin. The hypothesis to development of systemic immunity against skin cancers and thereby contribute to the outcome of the host-tumor interaction. This hypothesis is based on recent studies indicating that damage to the antigen presenting Langerhans cells in the skin resulting from ultraviolet (UV) irradiation prevents the development of T-cell mediated immunity to haptens applied to the irradiated skin and results in the development of hapten-specific suppressor T lymphocytes. Specifically, they will investigate whether impairing the activity of cutaneous antigen presenting cells by exposure of mice to UV radiation interferes with the development of systemic immunity to transplanted skin cancers or alters the pathogenesis of primary skin cancer in murine tumor models. In the transplanted tumor model, UV-induced progressor skin tumors are implanted into the pinna of the ear of syngeneic normal or UV-irradiated mice. The antigen presenting activity of cells recovered from the draining lymph nodes will be assessed using in vivo and in vitro assays of specific anti-tumor immunity, and the effect of UV-irradiation on tumor growth and progression will be determined. In the primary tumor model, they will investigate the effect of local UV-irradiation on the induction and progression of skin cancers that develop in transgenic mice carrying the bovine papilloma virus genome. In addition, they propose to continue their studies on the mechanism of cutaneous sensitization and its alteration by UV radiation using contact hypersensitivity to a fluorescent hapten as a model system.
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