Linked Life Data

20691153

Source:http://linkedlifedata.com/resource/pubmed/id/20691153

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-9-6
pubmed:abstractText
Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing beta cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rgamma(null) mice. The selective destruction of pancreatic islet beta cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total beta-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the beta cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet beta cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4(+) T cell infiltration and clonal expansion, and the mouse islet beta-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet beta cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
399
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
629-36
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model.
pubmed:affiliation
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. yongzhao@uic.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't