Source:http://linkedlifedata.com/resource/pubmed/id/12928371
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2003-8-20
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| pubmed:abstractText |
Early systemic treatment of nonobese diabetic mice with high doses of recombinant adeno-associated virus (rAAV) vector expressing murine IL-10 prevents type 1 diabetes. To determine the therapeutic parameters and immunological mechanisms underlying this observation, female nonobese diabetic mice at 4, 8, and 12 wk of age were given a single i.m. injection of rAAV-murine IL-10 (10(4), 10(6), 10(8), and 10(9) infectious units (IU)), rAAV-vector expressing truncated murine IL-10 fragment (10(9) IU), or saline. Transduction with rAAV-IL-10 at 10(9) IU completely prevented diabetes in all animals injected at all time points, including, surprisingly, 12-wk-old animals. Treatment with 10(8) IU provided no protection in the 12-wk-old injected mice, partial prevention in 8-wk-old mice, and full protection in all animals injected at 4 wk of age. All other treatment groups developed diabetes at a similar rate. The rAAV-IL-10 therapy attenuated pancreatic insulitis, decreased MHC II expression on CD11b+ cells, increased the population of CD11b+ cells, and modulated insulin autoantibody production. Interestingly, rAAV-IL-10 therapy dramatically increased the percentage of CD4+CD25+ regulatory T cells. Adoptive transfer studies suggest that rAAV-IL-10 treatment alters the capacity of splenocytes to impart type 1 diabetes in recipient animals. This study indicates the potential for immunomodulatory gene therapy to prevent autoimmune diseases, including type 1 diabetes, and implicates IL-10 as a molecule capable of increasing the percentages of regulatory cells in vivo.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
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| pubmed:issn |
0022-1767
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| pubmed:author |
pubmed-author:AtkinsonMark AMA,
pubmed-author:BruskoToddT,
pubmed-author:BurkhardtBrant RBR,
pubmed-author:Campbell-ThompsonMartha LML,
pubmed-author:Clare-SalzlerMichael JMJ,
pubmed-author:EllisTamir MTM,
pubmed-author:FlotteTerence RTR,
pubmed-author:GoudyKevin SKS,
pubmed-author:PowersMatthew AMA,
pubmed-author:SobelEric SES,
pubmed-author:SongSihongS,
pubmed-author:WasserfallCliveC
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| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
171
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2270-8
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12928371-Adenoviridae,
pubmed-meshheading:12928371-Animals,
pubmed-meshheading:12928371-Antibody Formation,
pubmed-meshheading:12928371-Autoantibodies,
pubmed-meshheading:12928371-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12928371-Dependovirus,
pubmed-meshheading:12928371-Diabetes Mellitus, Type 1,
pubmed-meshheading:12928371-Dose-Response Relationship, Immunologic,
pubmed-meshheading:12928371-Female,
pubmed-meshheading:12928371-Gene Therapy,
pubmed-meshheading:12928371-Genetic Vectors,
pubmed-meshheading:12928371-Immunity, Cellular,
pubmed-meshheading:12928371-Injections, Intramuscular,
pubmed-meshheading:12928371-Insulin Antibodies,
pubmed-meshheading:12928371-Interleukin-10,
pubmed-meshheading:12928371-Islets of Langerhans,
pubmed-meshheading:12928371-Mice,
pubmed-meshheading:12928371-Mice, Inbred C57BL,
pubmed-meshheading:12928371-Mice, Inbred NOD,
pubmed-meshheading:12928371-Receptors, Interleukin-2,
pubmed-meshheading:12928371-Recombination, Genetic,
pubmed-meshheading:12928371-T-Lymphocyte Subsets,
pubmed-meshheading:12928371-Time Factors
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion.
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| pubmed:affiliation |
Department of Pathology, Powell Gene Therapy Center, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, 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
|