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- W2068853909 abstract "522 Primary nonfunction (PNF) and early graft destruction are obstacles for the application of islet xenotransplantation in autoimmune type 1 diabetes. The first aim of this study was to investigate the role of autoimmune disease recurrence in PNF and xenograft survival in autoimmune NOD mice after PVG (c+) rat islet transplantation. The second aim was to examine the mediators of this early islet destruction. Results: Spontaneously diabetic autoimmune NOD mice had a shorter islet xenograft survival (5.4 ± 2.3 days) compared to chemically diabetic C57Bl/6 or old NOD mice (11.3 ± 1.2 days, p<0.01 and 9.7 ± 3.7 days, p<0.05). Also a higher incidence in PNF (44%) was noted in these autoimmune diabetic mice compared to non-autoimmune diabetic C57B1/6 or old NOD mice (10% and 29%). Analysis of cytokine mRNA levels locally in the xenografts showed clearly higher IL-1α, TNF-α and IL-6 levels in spontaneously diabetic autoimmune NOD mice 8 hours posttransplantation, rapidly decreasing after 16 hours. This early rise in macrophage-derived cytokines was mirrored by high mRNA levels of Fas ligand (Fas-L), a mediator of cell death in Fas expressing cells such as β cells. In the islet xenografts of the non-autoimmune diabetic mice (chemically diabetic C57Bl/6 or old NOD mice), elevated levels of IL-1α, TNF-α and IL-6 were only noted at 16 hours after transplantation. These high macrophage cytokine levels were now however not paralled by a rise in Fas-L mRNA. Another difference between autoimmune and non-autoimmune mice were the levels of the suppressive cytokine, TGF-β, being clearly higher (2 fold) in the non-autoimmune situation. T-cell cytokines (IL-2, IL-4, IL-12 and INF-γ) in islet xenografts of both autoimmune and non-autoimmune diabetic mice were absent or similar with background levels in the first 24 hours after transplantation, as were T cells on immunohistochemistry. In conclusion, these data suggest a role for the autoimmune memory in the occurrence of PNF and islet xenograft destruction in the spontaneously diabetic autoimmune NOD mice. The destruction of islets seems however to be mediated primarily by non-T cell types such as macrophages." @default.
- W2068853909 created "2016-06-24" @default.
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- W2068853909 date "1999-04-01" @default.
- W2068853909 modified "2023-09-26" @default.
- W2068853909 title "PRIMARY NONFUNCTION OF ISLET XENOGRAFTS IN SPONTANEOUSLY DIABETIC AUTOIMMUNE NOD MICE: CORRELATION WITH ELEVATED NON-T CELL CYTOKINES AND FASL EXPRESSION IN THE GRAFTS." @default.
- W2068853909 doi "https://doi.org/10.1097/00007890-199904150-00550" @default.
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