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• W1822922665 endingPage "e0127631" @default.
• W1822922665 startingPage "e0127631" @default.
• W1822922665 abstract "Restoration of endogenous insulin production by islet transplantation is considered a curative option for patients with type 1 diabetes. However, recurrent autoimmunity and alloreactivity cause graft rejection hindering successful transplantation. Here we tested whether transplant tolerance to allogeneic islets could be achieved in non-obese diabetic (NOD) mice by simultaneously tackling autoimmunity via antigen-specific immunization, and alloreactivity via granulocyte colony stimulating factor (G-CSF) and rapamycin (RAPA) treatment. Immunization with insB9-23 peptide alone or in combination with two islet peptides (IGRP206-214 and GAD524-543) in incomplete Freund's adjuvant (IFA) were tested for promoting syngeneic pancreatic islet engraftment in spontaneously diabetic NOD mice. Treatment with G-CSF/RAPA alone or in combination with insB9-23/IFA was examined for promoting allogeneic islet engraftment in the same mouse model. InsB9-23/IFA immunization significantly prolonged syngeneic pancreatic islet survival in NOD mice by a mechanism that necessitated the presence of CD4+CD25+ T regulatory (Treg) cells, while combination of three islet epitopes was less efficacious in controlling recurrent autoimmunity. G-CSF/RAPA treatment was unable to reverse T1D or control recurrent autoimmunity but significantly prolonged islet allograft survival in NOD mice. Blockade of interleukin-10 (IL-10) during G-CSF/RAPA treatment resulted in allograft rejection suggesting that IL-10-producing cells were fundamental to achieve transplant tolerance. G-CSF/RAPA treatment combined with insB9-23/IFA did not further increase the survival of allogeneic islets. Thus, insB9-23/IFA immunization controls recurrent autoimmunity and G-CSF/RAPA treatment limits alloreactivity, however their combination does not further promote allogeneic pancreatic islet engraftment in NOD mice." @default.
• W1822922665 created "2016-06-24" @default.
• W1822922665 creator A5030918187 @default.
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• W1822922665 date "2015-06-16" @default.
• W1822922665 modified "2023-10-18" @default.
• W1822922665 title "Combination of an Antigen-Specific Therapy and an Immunomodulatory Treatment to Simultaneous Block Recurrent Autoimmunity and Alloreactivity in Non-Obese Diabetic Mice" @default.
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• W1822922665 doi "https://doi.org/10.1371/journal.pone.0127631" @default.
• W1822922665 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4469694" @default.
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• W1822922665 hasPublicationYear "2015" @default.
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