title: Primary defect in UVB-induced systemic immunomodulation does not relate to immature or functionally impaired APCs in regional lymph nodes.
abstract: UVB irradiation of the shaved dorsal skin of mice can cause both local and systemic suppression of contact hypersensitivity responses; the former demonstrated by administration of the sensitizing Ag/hapten to the irradiated site and the latter by its administration at least 72 h later to distal unirradiated sites. The immunological basis of systemic immunomodulation is not clear. When haptens (trinitrochlorobenzene, FITC) were administered to the shaved ventral skin 4 days after irradiation (8 kJ/m(2)) to the shaved dorsum of BALB/c mice, CD11c(+)/FITC(+) cells in the skin-draining lymph nodes from control and irradiated mice produced on a per cell basis similar levels of IL-12 and PGE(2) were phenotypically mature and efficient at presenting FITC to lymphocytes from FITC-sensitized mice. Ag presentation by FACS-sorted CD11c(+) lymph node cells isolated 4 days after UVB irradiation was as efficient as were cells from unirradiated mice at presentation in vitro of an OVA peptide (OVA(323-339)) to CD4(+) cells from OVA-TCR-transgenic DO11.10 mice. Further, IFN-gamma levels were increased in the cultures containing CD11c(+) cells from UVB-irradiated mice, suggesting that inflammation may precede downstream immunosuppression. These results suggest that the primary cause of reduced contact hypersensitivity responses in mice in which UV irradiation and the sensitizing Ag are applied to different sites several days apart must originate from cells other than CD11c(+) APCs that directly or by production of soluble mediators (IL-12, PGE(2)) affect cellular responses in the nodes of UVB-irradiated mice.
authors.affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth.
authors.forename: Shelley
authors.initials: S
authors.lastname: Gorman
authors.forename: Jamie W-Y
authors.initials: JW
authors.lastname: Tan
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thomas
authors.forename: Scott L
authors.initials: SL
authors.lastname: Townley
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.forename: John J
authors.initials: JJ
authors.lastname: Finlay-Jones
authors.forename: Prue H
authors.initials: PH
authors.lastname: Hart
mesh_terms: D000287:Administration, Topical; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000528:radiation effects; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects*; D039521:CD11c Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology* / Q000528:radiation effects*; D002465:Cell Movement / Q000276:immunology / Q000528:radiation effects; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology / Q000528:radiation effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000378:metabolism / Q000528:radiation effects; D006241:Haptens / Q000008:administration & dosage / Q000096:biosynthesis / Q000528:radiation effects; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000502:physiology / Q000528:radiation effects*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology / Q000528:radiation effects; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D039521:CD11c Antigen; D006241:Haptens; D007155:Immunologic Factors; D018664:Interleukin-12; D016650:Fluorescein-5-isothiocyanate; D015232:Dinoprostone; D010853:Picryl Chloride