Effect of IL-12 on immune suppression and suppressor cell induction by ultraviolet radiation.
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.
Schmitt
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Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Owen-Schaub
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Ullrich
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SE
D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology* / Q000528:radiation effects*; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D018664:Interleukin-12