Linked Life Data

17376836

Source:http://linkedlifedata.com/resource/pubmed/id/17376836

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-5-16
pubmed:abstractText
Rodent immune-mediated diabetes model studies have advanced understanding of beta cell-specific T cell responses, and the testing of therapeutic approaches. We have used an inducible diabetes model based on rat insulin promotor (RIP)-driven expression of CD80 (B7-1) on pancreatic beta cells. Using these mice, we have established that immunizing with a single autoantigen can promote progressive islet inflammation and eventually T cell-mediated diabetes. We now describe a potent immunization protocol using peptide-pulsed mature dendritic cells (DCs) to examine peptide epitopes derived from endogenous (preproinsulin) and transgenically expressed beta cell antigens, namely lymphocytic choriomeningitis virus glycoprotein (LCMV-GP). LCMV-GP epitopes efficiently promote beta cell destruction, and the autoantigenic peptide concentration used to load the DCs correlates directly with diabetes onset. The system allowed us to assess cytotoxic T cell (CTL) fine specificity by immunizing with DCs presenting altered peptide ligands (APLs) of the dominant LCMV-GP epitope, gp33. Finally, using an adoptive transfer system, we tested alternative in vitro T cell activation conditions, including APLs and mitogens, for their impact on T cell effector function and diabetes onset. Our studies revealed a marked discrepancy between (inflammatory) effector functions and diabetes progression, thus emphasizing the importance of structural identity between sensitizing and target epitope and the context of initial T cell activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
132-42
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Cytotoxic T cell-mediated diabetes in RIP-CD80 transgenic mice: autoantigen peptide sensitivity and fine specificity.
pubmed:affiliation
Diabetes Branch, NIDDK, NIH, 10 Center Drive, Bldg. 10-CRC, Room 5W-5888, Bethesda, MD 20892, USA. KlausP@intra.niddk.nih.gov
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural