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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-2-27
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pubmed:abstractText |
Islet transplantation represents a potential cure for type 1 diabetes, yet persistent autoimmune and allogeneic immunities currently limit its clinical efficacy. For alleviating the autoimmune destruction of transplanted islets, newly diagnosed NOD mice were provided a single intramuscular injection of recombinant adeno-associated viral vector encoding murine IL-10 (rAAV-IL-10) 4 weeks before renal capsule delivery of 650 syngeneic islets. A dose-dependent protection of islet grafts was observed. Sixty percent (3 of 5) of NOD mice that received a transduction of a high-dose (4 x 10(9) infectious units) rAAV-IL-10 remained normoglycemic for at least 117 days, whereas diabetes recurred within 17 days in mice that received a low-dose rAAV-IL-10 (4 x 10(8) infectious units; 5 of 5) as well as in all of the control mice (5 of 5 untreated and 4 of 4 rAAV-green fluorescent protein-transduced). Serum IL-10 levels positively correlated with prolonged graft survival and were negatively associated with the intensity of autoimmunity. The mechanism of rAAV-IL-10 protection involved a reduction of lymphocytic infiltration as well as induction of antioxidant enzymes manganese superoxide dismutase and heme oxygenase 1 in islet grafts. These studies support the utility of immunoregulatory cytokine gene therapy delivered by rAAV for preventing autoimmune disease recurrence in transplant-based therapies for type 1 diabetes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0012-1797
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pubmed:author |
pubmed-author:AgarwalAnupamA,
pubmed-author:AtkinsonMark AMA,
pubmed-author:BruskoToddT,
pubmed-author:Campbell-ThompsonMarthaM,
pubmed-author:CrawfordJames MJM,
pubmed-author:EllisTamir MTM,
pubmed-author:FlotteTerenceT,
pubmed-author:GoudyKevinK,
pubmed-author:InverardiLucaL,
pubmed-author:MolanoR DamarisRD,
pubmed-author:NickHarryH,
pubmed-author:PileggiAntonelloA,
pubmed-author:PoggioliRaffaellaR,
pubmed-author:PowersMatthewM,
pubmed-author:RicordiCamilloC,
pubmed-author:Scott-JorgensenMardaM,
pubmed-author:WasserfallCliveC,
pubmed-author:ZahrElsieE,
pubmed-author:ZhangY ClareYC
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pubmed:issnType |
Print
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
708-16
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12606512-Animals,
pubmed-meshheading:12606512-Autoimmunity,
pubmed-meshheading:12606512-Dependovirus,
pubmed-meshheading:12606512-Diabetes Mellitus, Type 1,
pubmed-meshheading:12606512-Gene Expression,
pubmed-meshheading:12606512-Gene Therapy,
pubmed-meshheading:12606512-Genetic Vectors,
pubmed-meshheading:12606512-Graft Survival,
pubmed-meshheading:12606512-Green Fluorescent Proteins,
pubmed-meshheading:12606512-Heme Oxygenase (Decyclizing),
pubmed-meshheading:12606512-Heme Oxygenase-1,
pubmed-meshheading:12606512-Inflammation,
pubmed-meshheading:12606512-Interleukin-10,
pubmed-meshheading:12606512-Islets of Langerhans,
pubmed-meshheading:12606512-Islets of Langerhans Transplantation,
pubmed-meshheading:12606512-Luminescent Proteins,
pubmed-meshheading:12606512-Lymphocytes,
pubmed-meshheading:12606512-Membrane Proteins,
pubmed-meshheading:12606512-Mice,
pubmed-meshheading:12606512-Mice, Inbred NOD,
pubmed-meshheading:12606512-Muscle, Skeletal,
pubmed-meshheading:12606512-Recurrence,
pubmed-meshheading:12606512-Superoxide Dismutase
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pubmed:year |
2003
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pubmed:articleTitle |
Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice.
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pubmed:affiliation |
Department of Pathology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610-0275, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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