title: Systemic low-dose UVB inhibits CD8 T cells and skin inflammation by alternative and novel mechanisms.
abstract: Exposure to UVB radiation before antigen delivery at an unirradiated site inhibits functional immunological responses. Mice treated dorsally with suberythemal low-dose UVB and immunized with ova in abdominal skin generated ova-specific CD8 T cells with a significantly decreased activation, expansion, and cytotoxic activity compared with unirradiated mice. UVB also impaired the delayed-type hypersensitivity (DTH) reaction to ova. Transfer of CD4⁺CD25⁺cells from UVB-exposed mice did not suppress the ova-specific CD8 T-cell response or DTH reaction in unexposed mice, confirming that systemic low-dose UVB does not induce long-lived functional regulatory CD4⁺CD25⁺ T cells. Repairing cyclobutane pyrimidine dimer-type DNA damage and blocking aryl hydrocarbon receptor signaling also did not reverse the immunosuppressive effect of UVB on ova-specific CD8 T cells and DTH, suggesting that cyclobutane pyrimidine dimers and the aryl hydrocarbon receptor are not required in systemic low-dose UVB-induced immunosuppression. The known UVB chromophore, cis-urocanic acid, and reactive oxygen species triggered the inhibition of DTH caused by UVB, but they were not involved in the modulation of CD8 T cells. These findings indicate that systemic low-dose UVB impedes the primary response of antigen-specific CD8 T cells by a novel mechanism that is independent of pathways known to be involved in systemic suppression of DTH.
authors.affiliation: Discipline of Dermatology, Central Clinical School, Bosch Institute, Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Sabita
authors.initials: S
authors.lastname: Rana
authors.forename: Linda Joanne
authors.initials: LJ
authors.lastname: Rogers
authors.forename: Gary Mark
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006968:Hypersensitivity, Delayed / Q000150:complications / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011740:Pyrimidine Dimers / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology* / Q000528:radiation effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D011740:Pyrimidine Dimers; D018336:Receptors, Aryl Hydrocarbon; D010047:Ovalbumin; D014560:Urocanic Acid