Linked Life Data

19383625

Source:http://linkedlifedata.com/resource/pubmed/id/19383625

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-7-7
pubmed:abstractText
The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance; however, its role in autoimmune diabetes is unknown. In this study, we show that anti-BTLA mAb 6F7 selectively depleted pathogenic B and CD4+ T(H) cells; enhanced the proportion of cells with the forkhead box p3+ PD-1+CD4+ regulatory T phenotype; and increased the production of potentially protective (IL-10) and detrimental (IL-2, IFN-gamma) cytokines in NOD mice. As interactions between BTLA and PD-1 coinhibitory pathways have been described in the cardiac allograft model, we also investigated if these pathways may have significant interaction in autoimmune diabetes. Anti-BTLA inhibited anti-PD-1-potentiated total IL-12 (p40+p70) production, suggesting the possibility that anti-BTLA may have a greater effect in the setting of anti-PD-1-triggered diabetes. To test this, NOD mice at 4 and 10 weeks of age were treated with anti-BTLA mAb, anti-PD-1 mAb, both mAb, or isotype control and were monitored for diabetes development. Although anti-BTLA mAb delayed diabetes onset significantly in 10- but not 4-week-old NOD mice, anti-BTLA mAb attenuated anti-PD-1-induced diabetes in both age groups. Hence, strategies targeting BTLA+ lymphocytes or therapies enhancing the BTLA-negative cosignal may prove valuable in treating autoimmune diabetes.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1938-3673
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-51
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
BTLA targeting modulates lymphocyte phenotype, function, and numbers and attenuates disease in nonobese diabetic mice.
pubmed:affiliation
Surgical Medical Research Institute, Department of Surgery, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't