Effect of IL-12 on immune suppression and suppressor cell induction by ultraviolet radiation.

Abstract

The carcinogenic potential of UV radiation (the primary cause of nonmelanoma skin cancer) is associated with its ability to suppress cell-mediated immune responses. Previous studies have shown that this UV-induced immune suppression is caused by the secretion of immunosuppressive cytokines such as IL-10. Because the effects of IL-10 on the immune response are countered by IL-12, we injected irradiated mice with IL-12 to determine whether it could overcome UV-induced immune suppression. Administration of IL-12 blocked the suppression of delayed-in-time hypersensitivity reactions observed in UV-irradiated animals. Moreover, IL-12 prevented the induction of suppressor T cells, in that adoptive transfer of spleen cells from UV-irradiated mice treated with IL-12 had no effect on the immune response of the recipient mice, whereas transfer of spleen cells from UV-irradiated mice treated with the vehicle inhibited the immune response. In addition, IL-12 neutralized the activity of UV-induced suppressor T cells. Although the adoptive transfer of UV-induced suppressor T cells from irradiated mice suppressed the immune response of the recipient mice, treatment of the recipient mice with IL-12 following the adoptive transfer overcame the immune suppression. The results of these experiments demonstrate that IL-12 can overcome UV-induced immune suppression by preventing the induction of, as well as neutralizing the activity of pre-formed suppressor T cells.