Ultraviolet (UV) light treatment of donor islets has been shown to be effective for the prolongation of islet allograft survival in rodent models. This study evaluated UV as an immunomodulator of canine islets. The effects of UV irradiation on islet secretory function in vitro revealed a trend of increasing basal insulin release with increasing doses of UV and a corresponding significant decrease in glucose-mediated insulin release (expressed as percentage of basal fractional insulin release) beginning at UV light exposures of 200–300 J/m2 (n = 3, P < 0.05). Proliferative responses to UV-irradiated allogeneic peripheral blood leukocytes and islets were significantly decreased by 53–112% (P < 0.05) in 27 of 29 mixed-lymphocyte cultures and by 35–74% (P < 0.05) in 4 of 5 mixed-lymphocyte islet culture experiments, respectively, beginning at 200–600 J/m2. Autotransplantation of nonirradiated (n = 8) and irradiated islets (600 J/m2n = 6) resulted in a 1-mo graft survival rate of 75% for the control group and 50% for the irradiated group. Allotransplantation of irradiated islets (600 J/m2) into either nonimmunosuppressed recipients (1 donor to 1 recipient, n = 8) or recipients of subimmunosuppressive doses of cyclosporin (2 donors to 1 recipient, n = 4) resulted in 100% rejection by day 10. In contrast, when islets were cultured for 24 h postirradiation and transplanted into cyclosporin-treated pancreatectomized recipients (2 donors to 1 recipient), 3 of 7 grafts were prolonged beyond day 10 to days 16, 26, and >100. We conclude that direct UV irradiation of islets decreases canine islet immunogenicity and in combination with subtherapeutic dosages of cyclosporin can result in prolongation of islet allograft survival in this large-animal model.

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