Identification of Donor Origin and Condition of Transplanted Islets in Situ in the Liver of a Type 1 Diabetic Recipient
العنوان: | Identification of Donor Origin and Condition of Transplanted Islets in Situ in the Liver of a Type 1 Diabetic Recipient |
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المؤلفون: | Cornelis R. van der Torren, Ernst-Jan T van 't Wout, Jessica S Suwandi, Pieter Gillard, Frans H.J. Claas, Godelieve Swings, Zhidong Ling, DaHae Lee, Pieter In 'T Veld, Gaby Duinkerken, Bart O. Roep, Bart Keymeulen, Arend Mulder |
المساهمون: | Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, Experimental Pathology |
المصدر: | Cell Transplantation, Vol 26 (2017) Cell Transplantation, 26(1), 1-9 |
بيانات النشر: | SAGE Publishing, 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | 0301 basic medicine, CD8-Positive T-Lymphocytes/metabolism, Pathology, type 1 diabetes, Islets of Langerhans Transplantation, lcsh:Medicine, Autoimmunity, 030230 surgery, Autoimmunity/immunology, CD8-Positive T-Lymphocytes, 0302 clinical medicine, biomedical engineering, Medicine, Cytotoxic T cell, Islet transplantation, Kidney, geography.geographical_feature_category, Middle Aged, Islet, Tissue Donors, Type 1 diabetes, medicine.anatomical_structure, Liver, Diabetes Mellitus, Type 1/immunology, Female, Islets of Langerhans Transplantation/immunology, Pancreas, Liver/metabolism, medicine.medical_specialty, endocrine system, Histocompatibility Antigens Class I/immunology, Peripheral blood mononuclear cell, Article, 03 medical and health sciences, Diabetes mellitus, Humans, Transplantation, Homologous, Alloreactivity, geography, business.industry, Histocompatibility Antigens Class I, lcsh:R, Cell Biology, medicine.disease, HLA Mismatch, Pancreas/immunology, Transplantation, 030104 developmental biology, Diabetes Mellitus, Type 1, business, transplantation |
الوصف: | Transplantation of islet allografts into type 1 diabetic recipients usually requires multiple pancreas donors to achieve insulin independence. This adds to the challenges of immunological monitoring of islet transplantation currently relying on surrogate immune markers in peripheral blood. We investigated donor origin and infiltration of islets transplanted in the liver of a T1D patient who died of hemorrhagic stroke 4 months after successful transplantation with two intraportal islet grafts combining six donors. Immunohistological staining for donor HLA using a unique panel of human monoclonal HLA-specific alloantibodies was performed on liver cryosections after validation on cryopreserved kidney, liver, and pancreas and compared with auto- and alloreactive T-cell immunity in peripheral blood. HLA-specific staining intensity and signal-to-noise ratio varied between tissues from very strong on kidney glomeruli, less in liver, kidney tubuli, and endocrine pancreas to least in exocrine pancreas, complicating the staining of inflamed islets in an HLA-disparate liver. Nonetheless, five islets from different liver lobes could be attributed to donors 1, 2, and 5 by staining patterns with multiple HLA types. All islets showed infiltration with CD8+ cytotoxic T cells that was mirrored by progressive alloreactive responses in peripheral blood mononuclear cells (PBMCs) to donors 1, 2, and 5 after transplantation. Stably low rates of peripheral islet autoreactive T-cell responses after islet infusion fit with a complete HLA mismatch between grafts and recipient and exclude the possibility that the islet-infiltrating CD8 T cells were autoreactive. HLA-specific immunohistochemistry can identify donor origin in situ and differentiate graft dysfunction and immunological destruction. ispartof: Cell Transplantation vol:26 issue:1 pages:1-9 ispartof: location:United States status: published |
وصف الملف: | application/pdf; Print-Electronic |
اللغة: | English |
تدمد: | 1555-3892 0963-6897 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03120b927374e3d4310f24a9d03e09a5Test https://doaj.org/article/4fc08ec296f34a08bf92a0beb0387133Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....03120b927374e3d4310f24a9d03e09a5 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15553892 09636897 |
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