title: Mechanisms underlying the suppression of established immune responses by ultraviolet radiation.
abstract: The ultraviolet radiation present in sunlight is immune suppressive. Recently we showed that solar-simulated ultraviolet radiation (ultraviolet A + B; 295-400 nm), applied after immunization, suppressed immunologic memory and the elicitation of delayed-type hypersensitivity to the common opportunistic pathogen, Candida albicans. Further, we found that wavelengths in the ultraviolet A region of the solar spectrum (320-400 nm), devoid of ultraviolet B, were equally effective in activating immune suppression as ultraviolet A + B radiation. Here we report on the mechanisms involved. Maximal immune suppression was found when mice were exposed to solar-simulated ultraviolet radiation 7-9 d post immunization. No immune suppression was found in ultraviolet-irradiated mice injected with monoclonal anti-interleukin-10 antibody, or mice exposed to solar-simulated ultraviolet radiation and injected with recombinant interleukin-12. Suppressor lymphocytes were found in the spleens of mice exposed to ultraviolet A + B radiation. In addition, antigen-specific suppressor T cells (CD3+, CD4+, DX5+) were found in the spleens of mice exposed to ultraviolet A radiation. Applying liposomes containing bacteriophage T4N5 to the skin of mice exposed to solar-simulated ultraviolet A + B radiation, or mice exposed to ultraviolet A radiation, blocked immune suppression, demonstrating an essential role for ultraviolet-induced DNA damage in the suppression of established immune reactions. These findings indicate that overlapping immune suppressive mechanisms are activated by ultraviolet A and ultraviolet A + B radiation. Moreover, our findings demonstrate that ultraviolet radiation activates similar immunologic pathways to suppress the induction of, or the elicitation of, the immune response.
authors.affiliation: Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Dat X
authors.initials: DX
authors.lastname: Nghiem
authors.forename: Nasser
authors.initials: N
authors.lastname: Kazimi
authors.forename: David L
authors.initials: DL
authors.lastname: Mitchell
authors.forename: Arie A
authors.initials: AA
authors.lastname: Vink
authors.forename: Honnavara N
authors.initials: HN
authors.lastname: Ananthaswamy
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Kripke
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004249:DNA Damage / Q000276:immunology; D004260:DNA Repair / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007107:Immune System / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects*; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013472:Sunlight / Q000009:adverse effects; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D016753:Interleukin-10; D018664:Interleukin-12