title: UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR+ epidermal macrophage induction, and Langerhans cell depletion.
abstract: Increasing UVB radiation at the earth's surface might have adverse effects on in vivo immunologic responses in humans. We prospectively randomized subjects to test whether epicutaneous immunization is altered by prior administration of biologically equalized doses of UV radiation. Multiple doses of antigens on upper inner arm skin (UV protected) were used to elicit contact sensitivity responses, which were quantitated by measuring increases in skin thickness. If a dose of UVB sufficient to induce redness (erythemagenic) was administered to the immunization site prior to sensitization with dinitrochlorobenzene (DNCB), we noted a marked reduction in the degree of sensitization (P less than 0.0006) that was highly dose responsive (r = 0.98). Even suberythemagenic UV (less than a visible sunburn) resulted in a decreased frequency of strongly positive responses (32%) as compared to controls (73%) (P = 0.019). The rate of immunologic tolerance to DNCB (active suppression of a subsequent repeat immunization) in the groups that were initially sensitized on skin receiving erythemagenic doses of UV was 31% (P = 0.0003). In addition, a localized moderate sunburn appeared to modulate immunization with diphenylcyclopropenone through a distant, unirradiated site (41% weak responses) as compared to the control group (9%) (P = 0.05). Monitoring antigen presenting cell content in the epidermis revealed that erythemagenic regimens induced CD1a-DR+ macrophages and depleted Langerhans cells. In conclusion, relevant and even subclinical levels of UV exposure have significant down modulatory effects on the ability of humans to generate a T-cell-mediated response to antigens introduced through irradiated skin.
authors.affiliation: Department of Dermatology, University of Michigan, Ann Arbor 48109.
authors.forename: K D
authors.initials: KD
authors.lastname: Cooper
authors.forename: L
authors.initials: L
authors.lastname: Oberhelman
authors.forename: T A
authors.initials: TA
authors.lastname: Hamilton
authors.forename: O
authors.initials: O
authors.lastname: Baadsgaard
authors.forename: M
authors.initials: M
authors.lastname: Terhune
authors.forename: G
authors.initials: G
authors.lastname: LeVee
authors.forename: T
authors.initials: T
authors.lastname: Anderson
authors.forename: H
authors.initials: H
authors.lastname: Koren
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1; D003877:Dermatitis, Contact / Q000276:immunology*; D004137:Dinitrochlorobenzene / Q000276:immunology; D004307:Dose-Response Relationship, Radiation; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000528:radiation effects*; D007109:Immunity / Q000528:radiation effects*; D007111:Immunity, Cellular; D007801:Langerhans Cells / Q000276:immunology; D008262:Macrophage Activation; D012867:Skin / Q000528:radiation effects*; D013471:Sunburn / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; D004137:Dinitrochlorobenzene; D006684:HLA-DR Antigens