To circumvent rejection of allogeneic pancreatic islet grafts, we have examined the use of ultraviolet (UV) irradiation to inactivate allostimulatory cells in blood prior to their use for the induction of donor-specific tolerance and to decrease the immunogenicity of pancreatic islets by direct UV irradiation. UVB (280-320 nm) irradiation of blood can effectively abrogate lymphocyte stimulatory capacity in an MLC, while subsequent transfusions of appropriately UV irradiated blood have indefinitely prolonged islet allograft survival in the Lewis to ACI rat strain combination (greater than 250 days), without the use of immunosuppressive agents. This treatment is donor specific in that third-party W/F islet allograft survival is not prolonged in ACI rats transfused with UV-treated Lewis blood (MST, 7.5 days). When W/F rats are used as donors of blood, moderate prolongation of W/F islet allograft survival is obtained (MST of 21±12 days). When non-UV-treated W/F blood is transfused, rejection of W/F islets is accelerated (MST of 2 days versus no treatment control of 6.5 days) in the ACI recipient. UV irradiation of rat dendritic cells can completely abrogate their powerful stimulatory activity in an MLC at a dose of 900 J/m2. Rat islets subjected to this same dose of UV irradiation do not exhibit any alteration in their endocrine function when transplanted into syngeneic diabetic animals. UV irradiated (900 J/m2) Lewis islets transplanted into non-immunosuppressed ACI rats showed marked prolongation of survival (greater than 80 days). We conclude that UV irradiation is effective in immuno-alteration of the stimulatory cells in blood and can selectively decrease immunogenicity of pancreatic islets without being deleterious to their endocrine function. Both these methods are readily applicable to islet transplantation in other animals and eventually in humans.
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