|Author||James, R. F. ♦ Lake, S. P. ♦ Chamberlain, J. ♦ Thirdborough, S. ♦ Bassett, P. D. ♦ Mistry, N. ♦ Bell, P. R.|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT. ♦ IMMUNITY ♦ RADIOINDUCTION ♦ IMMUNOSUPPRESSIVE DRUGS ♦ RADIOSENSITIVITY EFFECTS ♦ PANCREAS ♦ TRANSPLANTS ♦ DIABETES MELLITUS ♦ DOSE-RESPONSE RELATIONSHIPS ♦ GAMMA RADIATION ♦ LEUKOCYTES ♦ LOW DOSE IRRADIATION ♦ NERVE CELLS ♦ RATS ♦ SURVIVAL TIME ♦ ANIMAL CELLS ♦ ANIMALS ♦ BIOLOGICAL MATERIALS ♦ BLOOD ♦ BLOOD CELLS ♦ BODY ♦ BODY FLUIDS ♦ DIGESTIVE SYSTEM ♦ DISEASES ♦ DRUGS ♦ ELECTROMAGNETIC RADIATION ♦ ENDOCRINE DISEASES ♦ ENDOCRINE GLANDS ♦ GLANDS ♦ IONIZING RADIATIONS ♦ IRRADIATION ♦ MAMMALS ♦ MATERIALS ♦ METABOLIC DISEASES ♦ ORGANS ♦ RADIATIONS ♦ RODENTS ♦ SOMATIC CELLS ♦ VERTEBRATES ♦ Radiation Effects on Animals- Animals|
|Abstract||In this study we have examined the use of low-dose gamma-irradiation for the reduction of islet immunogenicity in the strong allogeneic combination of WAG rat islets transplanted into diabetic AUG recipients. First, we determined that gamma-irradiation reduced immunogenicity in vitro by use of a modified MLR with WAG islets as stimulators and AUG splenocytes as responders. We then determined the maximum dose of gamma-irradiation that could be used (250 rads) before islet function was affected. As 250 rads islet pretreatment alone was ineffective in prolonging allograft survival, we combined the pretreatment with a short course (days 0, 1, 2; 30 mg/kg) of cyclosporine. We found that CsA was only effective in significantly prolonging allograft survival when given subcutaneously in olive oil. The CsA treatment alone gave a significantly prolonged survival time for the islet allografts (median, 37 days vs. 6 days for controls), but when combined with the 250 rads islet pretreatment a synergistic effect was seen with 100% becoming long-term survivors (greater than 100 days). The long-term surviving AUG rats from both the CsA alone group and the CsA plus 250 rads pretreated islets group were challenged with WAG dendritic cells (DC). The islets from the 250 rads pretreated group were subsequently rejected (day 6) while the CsA alone group were not affected. The role of low dose gamma-irradiation when combined with CsA treatment of islet graft recipients in inducing specific unresponsiveness will be discussed.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Organization||Leicester Royal Infirmary (England)|
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