Ultraviolet (UV) irradiation in vivo suppresses cell-mediated immunity to a variety of antigens and may be critical in UV carcinogenesis, preventing the immune rejection of highly antigenic UV tumors. Our most recent investigations have found a strain difference in susceptibility to UV suppression. C57BL/6 and related mice are nearly 4 fold more sensitive to systemic UV-induced suppression of contact hypersensitivity (CHS) than are 5 other unrelated mouse strains. We propose to investigate this increased UV sensitivity, since it may provide an important tool for further dissection of the mechanism of UV suppression, and may provide a model to identify factors responsible for sensitivity to certain UV-related diseases e.g. skin cancer and some forms of autoimmune disease. We wish to establish if UV suppression of CHS in BL/6 mice has, except for the dose response, similar characteristics to those we previously described for BALB/c mice i.e. is due to UVB, has similar kinetics, is independent of dose rate and of dose fractionation, is associated with a splenic antigen presenting cell alteration and the generation of antigen specific suppressor T cells. We propose to use 3 narrow bands of UV from our unique monochromator source to establish if their relative effectiveness at immunosuppression in similar in BL/6 mice to that established for BALB/c mice. Our previous studies provided evidence that UV suppression is initiated by a process involving the UV-induced isomerization from the trans to the cis isomer of a photoreceptor molecule urocanic acid (UCA) in the stratum corneum. We propose to compare the dose response for the formation of cis UCA and the kinetics of its loss from the skin after UV and to compare the dose-response for suppression of CHS by cis UCA in BL/6 and BALB/c mice. Finally, once the characterization of UV induced suppression is completed, we propose to use genetic backcrossing between BL/6 and BALB/c mice to investigate the genetics of UV sensitivity. Establishing the existence of a gene(s) for enhanced susceptibility to UV suppression would provide a powerful tool for use in studies of UV carcinogenesis and of UV related autoimmune disease.
Showing the most recent 10 out of 13 publications
