title: Ultraviolet a irradiation of C57BL/6 mice suppresses systemic contact hypersensitivity or enhances secondary immunity depending on dose.
abstract: Ultraviolet radiation is the most common environmental carcinogen humans are exposed to. It is now known that in order for skin cancers to develop, both genetic damage and immunosuppression is required. Ultraviolet-induced immunosuppression is therefore a key contributor to the development of skin cancer. Little is known about the relative contributions of the different ultraviolet spectra (A and B), however. Therefore detailed ultraviolet dose-response curves for systemic suppression of contact hypersensitivity in two mouse strains were determined to examine the relative contributions of each of these spectral components of sunlight to primary and secondary immunity. Whereas ultraviolet B caused a linear dose-related immunosuppression in both C57BL/6 and Balb/c mice, only C57BL/6 mice were immunosuppressed by medium doses of ultraviolet A. At higher ultraviolet A doses, C57BL/6 mice were protected from immunosuppression, suggesting a genetic predisposition to ultraviolet-A-induced immunomodulation. Surprisingly, we found that, in contrast to primary immunosuppression, low dose ultraviolet A enhanced the secondary immune response, whereas ultraviolet B caused antigen-specific tolerance. When ultraviolet A and ultraviolet B were combined to mimic sunlight (solar-simulated ultraviolet), immunosuppression and tolerance were only observed over a narrow dose range as the memory-enhancing effect of low dose ultraviolet A and the immunoprotective effect of higher dose ultraviolet A prevented the suppressive effects of ultraviolet B. These studies suggest that complex relationships between ultraviolet dose, immunomodulation, spectra, and genetic background are likely to be important for skin cancer induction. We also describe for the first time that low doses of ultraviolet A are able to enhance secondary immunity, which has important implications for vaccination strategies.
authors.affiliation: Department of Medicine (Dermatology), Melanoma and Skin Cancer Research Institute, Sydney Cancer Center, Royal Prince Alfred Hospital at the University of Sydney, Australia.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Byrne
authors.forename: Nicole
authors.initials: N
authors.lastname: Spinks
authors.forename: Gary M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000818:Animals; D003877:Dermatitis, Contact / Q000517:prevention & control*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007108:Immune Tolerance / Q000528:radiation effects*; D007109:Immunity / Q000528:radiation effects*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014466:Ultraviolet Rays