Source:http://linkedlifedata.com/resource/pubmed/id/15585854
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2004-12-8
|
| pubmed:abstractText |
Autoimmunity presumably manifests as a consequence of a shortfall in the maintenance of peripheral tolerance by CD4(+)CD25(+) T regulatory cells (Tregs). However, the mechanism underlying the functional impairment of Tregs remains largely undefined. In this study a glutamic acid decarboxylase (GAD) diabetogenic epitope was expressed on an Ig to enhance tolerogenic function, and the resulting Ig-GAD expanded Tregs in both young and older insulitis-positive, nonobese diabetic (NOD) mice, but delayed autoimmune diabetes only in the former. Interestingly, Tregs induced at 4 wk of age had significant active membrane-bound TGF-beta (mTGF-beta) and sustained protection against diabetes, whereas Tregs expanded during insulitis had minimal mTGF-beta and could not protect against diabetes. The Tregs probably operate suppressive function through mTGF-beta, because Ab blockade of mTGF-beta nullifies protection against diabetes. Surprisingly, young Tregs that modulated pathogenic T cells maintained stable frequency over time in the protected animals, but decreased their mTGF-beta at the age of 8 wk. More strikingly, these 8-wk-old mTGF-beta-negative Tregs, which were previously protective, became unable to confer resistance against diabetes. Thus, a developmental decline in active mTGF-beta nullifies Treg function, leading to a break in tolerance and the onset of diabetes.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamate Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
173
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7308-16
|
| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15585854-Aging,
pubmed-meshheading:15585854-Amino Acid Sequence,
pubmed-meshheading:15585854-Animals,
pubmed-meshheading:15585854-Cell Differentiation,
pubmed-meshheading:15585854-Clone Cells,
pubmed-meshheading:15585854-Diabetes Mellitus, Type 1,
pubmed-meshheading:15585854-Down-Regulation,
pubmed-meshheading:15585854-Epitopes, T-Lymphocyte,
pubmed-meshheading:15585854-Female,
pubmed-meshheading:15585854-Glutamate Decarboxylase,
pubmed-meshheading:15585854-Membrane Proteins,
pubmed-meshheading:15585854-Mice,
pubmed-meshheading:15585854-Mice, Inbred NOD,
pubmed-meshheading:15585854-Mice, Knockout,
pubmed-meshheading:15585854-Mice, SCID,
pubmed-meshheading:15585854-Molecular Sequence Data,
pubmed-meshheading:15585854-Peptides,
pubmed-meshheading:15585854-T-Lymphocytes, Regulatory,
pubmed-meshheading:15585854-Transforming Growth Factor beta
|
| pubmed:year |
2004
|
| pubmed:articleTitle |
A sudden decline in active membrane-bound TGF-beta impairs both T regulatory cell function and protection against autoimmune diabetes.
|
| pubmed:affiliation |
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, 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
|