The objective of this proposal will be to address unresolved issues concerning the immunosuppressive effects of ultraviolet B (UVB) radiation human skin. We plan to test the hypothesis that UVB radiation mediates its effects on human cutaneous immune function, at least in part, by inhibiting the capacity of epidermal tissue to activate populations of T lymphocytes necessary for the development of cell-mediated immune responses. We will first compare the accessory function of unfractionated epidermal cell suspensions and purified Langerhans cells following in vitro exposure to various doses of UVB radiation in in vitro T lymphocyte proliferation assays. Different antigenic stimuli will be employed each of which provides complementary information regarding the mechanisms by which accessory cells activate T lymphocytes. In other studies, epidermal cell suspensions and purified Langerhans cells will be pretreated with cytokines or will be precultured before UVB exposure in an attempt to protect epidermal accessory function from the adverse effects of UVB radiation. Efforts will be made to assess the impact of UVB radiation on epidermal accessory signals, such as adhesion molecule expression and antigen processing, that are required for T cell activation. Studies will be conducted to define the molecular mechanisms by which ultraviolet radiation inhibits ICAM-1 expression. Finally, we will correlate the adverse effects of in vivo UVB radiation exposure on epidermal accessory function with inhibition in the development of contact hypersensitivity that occurs when attempts are made to immunize individuals to DNCB by applying it through UVB-irradiation skin. Knowledge obtained from these studies may help to define the effect of UVB exposure on cutaneous immunological processes and enhance our understanding of the role that this environmental agent plays in the pathogenesis of human disease.
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