We have examined the mechanism by which solar-simulated ultraviolet radiation (ssUV) suppresses memory immunity to nickel in allergic humans. In initial studies, we used inbred mice to determine the contribution of different wavebands to sunlight-induced immunosuppression. We found that low dose UVA can enhance memory, medium dose UVA (half the amount in one minimum erythemal dose of ssUV) is immunosuppressive, but higher doses protect from UVB. This is genetically dependent, as it is not observed in all mouse strains. UVA caused a similar dose-related change in recall immunity in humans. ssUV dose responses determined the limits of protection provided by sunscreens from immunosuppression in humans. Immune protection factors calculated from these data correlated with UVA protection, but not with sun protection factor, showing that in commercial sunscreens that provide good UVB protection, UVA protection limits prevention of immunosuppression. N(G)-monomethyl-l-arginine acetate (l-NMMA) was used to inhibit nitric oxide (NO) production and T4N5 liposomes containing T4 endonuclease V to enhance DNA repair. Sub-erythemal ssUV caused a dose-related local suppression of recall immunity to nickel in humans. l-NMMA and the liposomes protected the nickel reaction, suggesting that NO and DNA damage are mediators of UV-induced immunosuppression in humans.

Many studies support the role of ultraviolet B in sunlight-induced alteration of the cutaneous immune system. The role of ultraviolet A is less clear, particularly in humans. The aim of this study was to determine the effect of additional ultraviolet A on solar-simulated ultraviolet-induced suppression of recall responses to nickel in humans. Immuno suppression dose-responses were induced in volunteers by exposure to solar-simulated ultraviolet radiation for four consecutive days. The ultraviolet A radiation dose was increased daily by providing additional high-dose ultraviolet A either before, or after the solar-simulated ultraviolet radiation. These ultraviolet A doses can be readily achieved through a sunscreen. Two different ultraviolet A spectra were used; 320-400 nm and 330-400 nm. Ultraviolet A alone did not cause significant immunosuppression, but augmented solar-simulated ultraviolet radiation-induced immunosuppression. Additional ultraviolet A reduced the minimum dose of solar-simulated ultraviolet radiation that was immunosuppressive. Both ultraviolet A spectra had this effect, although photoaugmentation was less pronounced with the 330-400 nm spectrum. Ultraviolet A-induced immediate pigment darkening did not protect from solar-simulated ultraviolet radiation-induced immuno suppression.

We tested the hypothesis that DNA is a target for solar-simulated ultraviolet radiation (ssUVR)-induced suppression of the reactivation of memory immunity in humans. T4N5 liposomes contain the DNA repair enzyme T4 endonuclease V. This cleaves DNA at the site of ultraviolet radiation (UVR)-induced cyclobutane pyrimidine dimers (CPD), initiating DNA repair. It has previously been used to show that CPDs are a key molecular trigger for UVR-induced immunosuppression in mice. To determine whether CPD formation is involved in UVR immunosuppression in humans, nickel-allergic volunteers were irradiated with a range of doses of ssUVR. T4N5 or empty liposomes were then applied after irradiation. Nickel-induced recall immunity was assessed by reflectance spectrometry. T4N5 liposomes inhibited immunosuppression and prevented ssUVR from reducing the number of epidermal dendritic cells. T4N5 liposomes also reduced macrophage infiltration into irradiated epidermis. These studies show that enhanced removal of CPDs from human skin protects from immunosuppression, hence demonstrating that these photolesions are an important molecular event in ssUVR-induced immunosuppression in humans. CPDs also triggered loss of dendritic cells and infiltration by macrophages. It is possible that these changes to antigen presenting cells contribute to ssUVR induced suppression of recall immunity to nickel in humans.