Linked Life Data

20544729

Source:http://linkedlifedata.com/resource/pubmed/id/20544729

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-9-20
pubmed:abstractText
NOD mice spontaneously develop insulin-dependent diabetes around 10-40?wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward ? cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS(-/-) and ICOSL(-/-) NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4(+) and CD8(+) T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS(-/-) NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS(-/-) NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-4141
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2267-76
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20544729-Adoptive Transfer, pubmed-meshheading:20544729-Animals, pubmed-meshheading:20544729-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:20544729-Autoimmunity, pubmed-meshheading:20544729-Diabetes Mellitus, Type 1, pubmed-meshheading:20544729-Facial Nerve Diseases, pubmed-meshheading:20544729-Immune Tolerance, pubmed-meshheading:20544729-Inducible T-Cell Co-Stimulator Ligand, pubmed-meshheading:20544729-Inducible T-Cell Co-Stimulator Protein, pubmed-meshheading:20544729-Lymphocyte Activation, pubmed-meshheading:20544729-Mice, pubmed-meshheading:20544729-Mice, Inbred NOD, pubmed-meshheading:20544729-Mice, Knockout, pubmed-meshheading:20544729-Myositis, pubmed-meshheading:20544729-Proteins, pubmed-meshheading:20544729-T-Lymphocyte Subsets, pubmed-meshheading:20544729-T-Lymphocytes, Regulatory
pubmed:year
2010
pubmed:articleTitle
Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system.
pubmed:affiliation
INSERM U986, Hôpital Cochin/St Vincent de Paul, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't