Linked Life Data

11739540

Source:http://linkedlifedata.com/resource/pubmed/id/11739540

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2001-12-12
pubmed:abstractText
Type 1 diabetes in nonobese diabetic (NOD) mice is characterized by the infiltration of T and B cells into pancreatic islets. T cells bearing the TCR Vbeta3 chain are disproportionately represented in the earliest stages of islet infiltration (insulitis) despite clonal deletion of most Vbeta3(+) immature thymocytes by the mammary tumor virus-3 (Mtv-3) superantigen (SAg). In this report we showed that a high frequency of NOD Vbeta3(+) T cells that escape deletion are activated in vivo and that this phenotype is linked to the Mtv-3 locus. One potential mechanism of SAg presentation to peripheral T cells is by activated B cells. Consistent with this idea, we found that NOD mice harbor a significantly higher frequency of activated B cells than nondiabetes-prone strains. These activated NOD B cells expressed cell surface molecules consistent with APC function. At the molecular level, the IgH repertoire of activated B cells in NOD mice was equivalent to resting B cells, suggesting a polyclonal response in vivo. Genetic analysis of the activated B cell phenotype showed linkage to Idd1, the NOD MHC haplotype (H-2(g7)). Finally, Vbeta3(+) thymocyte deletion and peripheral T cell activation did not require B cells, suggesting that other APC populations are sufficient to generate both Mtv-3-linked phenotypes. These data provide insight into the genetic regulation of NOD autoreactive lymphocyte activation that may contribute to failure of peripheral tolerance and the pathogenesis of type I diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7169-79
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11739540-Animals, pubmed-meshheading:11739540-Antigens, CD, pubmed-meshheading:11739540-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:11739540-Antigens, Viral, pubmed-meshheading:11739540-B-Lymphocytes, pubmed-meshheading:11739540-Cells, Cultured, pubmed-meshheading:11739540-Chromosome Mapping, pubmed-meshheading:11739540-Clonal Deletion, pubmed-meshheading:11739540-Diabetes Mellitus, Type 1, pubmed-meshheading:11739540-Flow Cytometry, pubmed-meshheading:11739540-Genes, T-Cell Receptor beta, pubmed-meshheading:11739540-Immunoglobulin Variable Region, pubmed-meshheading:11739540-Lectins, C-Type, pubmed-meshheading:11739540-Lymphocyte Activation, pubmed-meshheading:11739540-Major Histocompatibility Complex, pubmed-meshheading:11739540-Mice, pubmed-meshheading:11739540-Mice, Inbred NOD, pubmed-meshheading:11739540-Proviruses, pubmed-meshheading:11739540-Receptors, Antigen, T-Cell, pubmed-meshheading:11739540-Superantigens, pubmed-meshheading:11739540-T-Lymphocytes
pubmed:year
2001
pubmed:articleTitle
Genetic control of T and B lymphocyte activation in nonobese diabetic mice.
pubmed:affiliation
Program in Developmental Biology, Hospital for Sick Children Research Institute, Department of Surgery, University of Toronto, Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't