Linked Life Data

16424193

Source:http://linkedlifedata.com/resource/pubmed/id/16424193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-1-20
pubmed:abstractText
beta cell replacement via islet or pancreas transplantation is currently the only approach to cure type 1 diabetic patients. Recurrent beta cell autoimmunity is a critical factor contributing to graft rejection along with alloreactivity. However, the specificity and dynamics of recurrent beta cell autoimmunity remain largely undefined. Accordingly, we compared the repertoire of CD8+ T cells infiltrating grafted and endogenous islets in diabetic nonobese diabetic mice. In endogenous islets, CD8+ T cells specific for an islet-specific glucose-6-phosphatase catalytic subunit-related protein derived peptide (IGRP206-214) were the most prevalent T cells. Similar CD8+ T cells dominated the early graft infiltrate but were expanded 6-fold relative to endogenous islets. Single-cell analysis of the TCR alpha and beta chains showed restricted variable gene usage by IGRP206-214-specific CD8+ T cells that was shared between the graft and endogenous islets of individual mice. However, as islet graft infiltration progressed, the number of IGRP206-214-specific CD8+ T cells decreased despite stable numbers of CD8+ T cells. These results demonstrate that recurrent beta cell autoimmunity is characterized by recruitment to the grafts and expansion of already prevalent autoimmune T cell clonotypes residing in the endogenous islets. Furthermore, depletion of IGRP206-214-specific CD8+ T cells by peptide administration delayed islet graft survival, suggesting IGRP206-214-specific CD8+ T cells play a role early in islet graft rejection but are displaced with time by other specificities, perhaps by epitope spread.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1637-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16424193-Animals, pubmed-meshheading:16424193-CD8-Positive T-Lymphocytes, pubmed-meshheading:16424193-Cell Movement, pubmed-meshheading:16424193-Cells, Cultured, pubmed-meshheading:16424193-Diabetes Mellitus, Type 1, pubmed-meshheading:16424193-Epitopes, T-Lymphocyte, pubmed-meshheading:16424193-Female, pubmed-meshheading:16424193-Glucose-6-Phosphatase, pubmed-meshheading:16424193-Graft Rejection, pubmed-meshheading:16424193-Islets of Langerhans, pubmed-meshheading:16424193-Islets of Langerhans Transplantation, pubmed-meshheading:16424193-Mice, pubmed-meshheading:16424193-Mice, Inbred BALB C, pubmed-meshheading:16424193-Mice, Inbred NOD, pubmed-meshheading:16424193-Mice, SCID, pubmed-meshheading:16424193-Mice, Transgenic, pubmed-meshheading:16424193-Peptide Fragments, pubmed-meshheading:16424193-Proteins, pubmed-meshheading:16424193-Receptors, Antigen, T-Cell
pubmed:year
2006
pubmed:articleTitle
Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.
pubmed:affiliation
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural