Source:http://linkedlifedata.com/resource/pubmed/id/17496235
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2007-7-30
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pubmed:abstractText |
In vivo induction of beta-cell apoptosis has been demonstrated to be effective in preventing type 1 diabetes in NOD mice. Based on the notion that steady-state cell apoptosis is associated with self-tolerance and the need for developing a more practical approach using apoptotic beta-cells to prevent type 1 diabetes, the current study was designed to investigate apoptotic beta-cells induced ex vivo in preventing type 1 diabetes. The NIT-1 cell line serves as a source of beta-cells. Apoptotic NIT-1 cells were prepared by ultraviolet B (UVB) irradiation. Three weekly transfusions of UVB-irradiated NIT-1 cells (1 x 10(5)/mouse) or PBS were used to determine whether transfusions of UVB-irradiated NIT-1 cells induce immune tolerance to beta-cell antigens in vivo and prevent type 1 diabetes. The suppression of anti-beta-cell antibodies, polarization of T-helper (Th) cells, and induction of regulatory T-cells by UVB-irradiated NIT-1 cell treatment were investigated. The transfusions of apoptotic NIT-1 cells suppress anti-beta-cell antibody development and induce Th2 responses and interleukin-10-producing regulatory type 1 cells. Importantly, this treatment significantly delays and prevents the onset of diabetes when 10-week-old NOD mice are treated. Adoptive transfer of splenocytes from UVB-irradiated NIT-1 cell-treated mice prevents diabetes caused by simultaneously injected diabetogenic splenocytes in NOD-Rag(-/-) mice. Moreover, the proliferation of adoptively transferred carboxyfluorescein diacetate succinimidyl ester-labeled beta-cell antigen-specific T-cell receptor-transgenic T-cells in UVB-irradiated NIT-1-cell treated mice is markedly suppressed. The transfusion of apoptotic beta-cells effectively protects against type 1 diabetes in NOD mice by inducing immune tolerance to beta-cell antigens. This approach has great potential for immune intervention for human type 1 diabetes.
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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
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pubmed:month |
Aug
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pubmed:issn |
1939-327X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2116-23
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:17496235-Adoptive Transfer,
pubmed-meshheading:17496235-Age of Onset,
pubmed-meshheading:17496235-Animals,
pubmed-meshheading:17496235-Antigens,
pubmed-meshheading:17496235-Apoptosis,
pubmed-meshheading:17496235-Autoantibodies,
pubmed-meshheading:17496235-Cell Differentiation,
pubmed-meshheading:17496235-Cell Line,
pubmed-meshheading:17496235-Cells, Cultured,
pubmed-meshheading:17496235-Cytokines,
pubmed-meshheading:17496235-Diabetes Mellitus, Type 1,
pubmed-meshheading:17496235-Immune Tolerance,
pubmed-meshheading:17496235-Insulin-Secreting Cells,
pubmed-meshheading:17496235-Mice,
pubmed-meshheading:17496235-Mice, Inbred NOD,
pubmed-meshheading:17496235-Mice, Knockout,
pubmed-meshheading:17496235-T-Lymphocytes, Regulatory,
pubmed-meshheading:17496235-Th2 Cells
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pubmed:year |
2007
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pubmed:articleTitle |
Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice.
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pubmed:affiliation |
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA. xia@pathology.ufl.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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