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DOI: 10.1055/s-2007-979921
© Georg Thieme Verlag Stuttgart · New York
Ultraviolet Light Irradiation Reduces Human Islet Immunogenicity Without Altering Islet Function*
* This work was supported by a grant from the Nora Eccles Treadwell Foundation, the Jerry's Foundation and the Oberkoter Foundation** P.Y.B. was the recipient of a research fellowship from Eli Lilly International and from La Fondation pour la Recherche ThérapeutiquePublikationsverlauf
1994
1994
Publikationsdatum:
23. April 2007 (online)
Abstract
Allograft rejection is the major cause for failure in clinical islet transplantation for diabetic patients. A reduction of donor islet immunogenicity is potentially a useful approach for altering recipient's immune responses. Studies in animal models have shown the immunomodulatory properties of ultraviolet (UV)-B light that are beneficial for allograft survival. However, there is a narrow window between the doses required for immunomodulation and those toxic to β-cells. In addition, this window varies between one species to another. Our study was designed to determine, in vitro, the UV-B dose for human islets that effectively reduces immunogenicity and maintains islet viability and normal function. Islets were isolated from donor pancreas by collagenase digestion and density gradient centrifugation on Euro-Ficoll. Static incubation and perifusion tests were used to measure glucose-stimulated insulin release. Viability was also assessed by histology and function of UV-irradiated islets transplanted under the renal capsule of athymic mice. The immunogenicity of UV-treated islets was determined in vitro with mixed islet lymphocyte culture using healthy human peripheral blood lymphocytes as responders. At a dose of 300 J/m2, both functional assays detected no impairment of insulin release. At 500 J/m2, a slight decrease of stimulated insulin release was observed only in the perifusion system. At the levels of 600 and 900 J/m2, a clear alteration was observed in both basal and stimulated insulin release. Islets irradiated at 300 J/m2 and transplanted into athymic mice stained strongly for insulin and responded to high glucose challenge in in vivo perfusion performed at two weeks. The immunogenicity of UV-irradiated islets was significantly decreased by 43 - 81% at 300 J/m2 and 51 - 70% at 500 J/m2. This effect was still present when tested as late as 9 days after irradiation, but only if islets were irradiated immediately after isolation. We conclude that UV-B irradiation at a dose of 300 J/m2 can effectively reduce immunogenicity of human islets without adverse effects on β-cell survival and function. This low dose UV-B irradiation may be a realistic treatment of human islets prior to transplantation.
Key words
Ultraviolet-B - Human Islets - Islet Function - Islet Immunogenicity