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SUMMARYStudies in experimental models have implicated histamine and prostanoids in ultra-violet B ( UVB)-and cis-urocanic acid ( UCA)-induced systemic immunosuppression. This study examined the hypothesis that UVB irradiation and cis-UCA suppressed contact hypersensitivity responses to hapten by induction of histamine, which in turn evoked a prostanoid-dependent component of immunosuppression. BALB/c mice were administered with a cis-UCA monoclonal antibody, a combination of histamine types 1 and 2 receptor antagonists, or indomethacin. Mice were sensitized to 2,4,6-trinitrochlorobenzene (TNCB) on their ventral surface 5 days after UVB irradiation, or cis-UCA or histamine administration. Ears were challenged with TNCB 5 days later. Cis-UCA antibody inhibited the suppressive eÂects of UVB by approximately 60% and confirmed that suppression of contact hypersensitivity responses by UVB was due, at least in part, to mechanisms involving cis-UCA. Histamine suppressed contact hypersensitivity responses and the eÂects of cis-UCA and histamine were not cumulative, suggesting that cis-UCA and histamine signal largely through the same pathway. The immunosuppressive eÂects of histamine were not aÂected by the cis-UCA antibody, consistent with the model that histamine acts downstream of cis-UCA. Administration of histamine receptor antagonists and indomethacin each approximately halved the UVB-and cis-UCA-induced systemic suppression of contact hypersensitivity responses. The eÂects of the reagents that inhibited the action of histamine and prevented prostanoid production were not cumulative, and suggested involvement in the same pathway. These results support the involvement of cis-UCA, histamine and prostanoids, in a sequence, in UVB-induced systemic suppression of contact hypersensitivity responses. INTRODUCTIONwhich, in turn, initiates immunosuppressive signals. There is some evidence that DNA may be a UVB photoreceptor,6,7 Ultra-violet B ( UVB) irradiation (wavelength 280-320 nm) is but trans-urocanic acid (deaminated histidine), a molecular immunosuppressive and allows the growth of highly antigenic species located superficially in the stratum corneum of the skin UV-induced tumours.1,2 The immunosuppression can be both and which isomerizes to its cis form on UVB irradiation, has local and systemic, and results in reduced expression of contact also been implicated in the mechanisms whereby UV hypersensitivity (CHS) and delayed-type hypersensitivity irradiation generates systemic immunosuppression.8-12 Skin ( DTH) responses to a variety of antigens in mice and humans.painting or parenteral inoculation with cis-UCA can reduce Examination of the suppression of CHS responses to haptens systemic CHS responses and is associated with an alteration in experimental animals has allowed some dissection of the in antigen-presenting cell ability in vivo. However, in vitro mechanisms of the UVB-induced eÂects.2-4 studies have shown that the defect is not due to the direct As less than 10% of UVB irradiation reaches the dermis,5 eÂec...

UV radiation induces skin cancer primarily by its DNA-damaging properties, but also by its capacity to suppress the immune system. The photoisomer of urocanic acid (UCA), cis-UCA, is an important mediator of UV-induced immunosuppression and is involved in the inhibition of tumor immunity. The immunomodulatory cytokine IL-12 is known to counteract many of the immunosuppressive effects of UV radiation, including UV-induced immune tolerance. In this study, we addressed whether IL-12 also reverts the immunosuppressive activities of cis-UCA. Cis-UCA inhibits the ability of Langerhans cells to present tumor Ags for primary and secondary tumor immune responses. IL-12 treatment completely prevented the suppression by cis-UCA. IL-12 also protected mice from cis-UCA-induced suppression of contact hypersensitivity responses. To study the effects of cis-UCA on Ag-processing and Ag-presenting function in vitro, Langerhans cells were treated with UCA isomers and incubated with OVA or OVA peptide323–339 before exposure to OVA-specific transgenic T cells. Cis-, but not trans-UCA suppressed Ag presentation, which was completely reversed upon addition of IL-12. Since these findings suggest that cis-UCA may play an important role in photocarcinogenesis by inhibiting a tumor immune response, mice were chronically UVB irradiated to induce skin cancer. Whereas all mice in the control groups developed tumors, mice treated with a mAb with specificity for cis-UCA showed a significantly reduced tumor incidence. These data strongly indicate the importance of cis-UCA during photocarcinogenesis and support the concept of counteracting cis-UCA as an alternative strategy to prevent UV-induced skin cancer, possibly via the application of IL-12.

Ultraviolet B (UVB) irradiation of C3H mice causes suppression of delayed hypersensitivity and contact hypersensitivity (CH) to antigens encountered following exposure, and is accompanied by a reduction in Langerhans cell (LC) numbers in the epidermis, loss of epidermal antigen-presenting cell function, and accumulation of dendritic cells in lymph nodes draining the site of irradiation. Various photoreceptors and mediators of these changes have been proposed, one of which is cis-urocanic acid (cis-UCA) formed from the naturally occurring trans-UCA in the epidermis on UV irradiation. A monoclonal antibody that reacts with cis-UCA has become available recently and has been used in this study to clarify the role of UCA. Pretreatment of C3H mice with the monoclonal antibody abrogated the UVB-induced and cis-UCA-induced reduction in epidermal LC numbers. It also prevented the UV-induced suppression of epidermal antigen-presenting cell ability as measured by the mixed skin lymphocyte response. However, it had no effect on the accumulation of dendritic cells in lymph nodes draining the site of UV exposure. With regard to hypersensitivity responses, it did not prevent UV-induced suppression of CH to oxazolone at a range of concentrations but it restored to normal the UV-suppressed delayed hypersensitivity to herpes simplex virus, if administered before exposure. Thus cis-UCA is involved in some UV-induced changes in murine skin but not in others, where alternative mediators, such as tumor necrosis factor-alpha, may be more important.

Two bovine coronavirus (BCV) strains from diarrheic calf faeces were adapted to grow in HRT 18 cells and compared in immunofluorescence (IF), haemagglutination inhibition (HAI) and neutralisation (NT) tests with three other strains of BCV and a human coronavirus (HCV) strain obtained from other laboratories. Polyclonal antisera against these 6 viruses were raised in rabbits. No significant differences between viruses were detected by IF. In the HAI test the HCV strain was distinguishable from the 5 BCV strains and serological variation between the BCV strains was shown. HCV could be distinguished by NT test, but all BCV isolates were similar. Two monoclonal antibodies prepared against one of the BCV strains distinguished HCV in all three assays, and detected varying relationships between BCV strains.