Linked Life Data

15908957

Source:http://linkedlifedata.com/resource/pubmed/id/15908957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-6-6
pubmed:abstractText
Antigen therapy may hold great promise for the prevention of autoimmunity; however, most clinical trials have failed, suggesting that the principles guiding the choice of treatment remain ill defined. Here, we examine the antidiabetogenic properties of altered peptide ligands of CD8+ T cells recognizing an epitope of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP206-214), a prevalent population of autoreactive T cells in autoimmune diabetes. We show that islet-associated CD8+ T cells in nonobese diabetic mice recognize numerous IGRP epitopes, and that these cells have a role in the outcome of protocols designed to induce IGRP206-214-specific tolerance. Ligands targeting IGRP206-214-reactive T cells prevented disease, but only at doses that spared low-avidity clonotypes. Notably, near complete depletion of the IGRP206-214-reactive T-cell pool enhanced the recruitment of subdominant specificities and did not blunt diabetogenesis. Thus, peptide therapy in autoimmunity is most effective under conditions that foster occupation of the target organ lymphocyte niche by nonpathogenic, low-avidity clonotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1078-8956
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
645-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low-affinity peptide.
pubmed:affiliation
Julia McFarlane Diabetes Research Centre, University of Calgary, Faculty of Medicine, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't