Linked Life Data

15634884

Source:http://linkedlifedata.com/resource/pubmed/id/15634884

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-1-6
pubmed:abstractText
IL-10, a powerful anti-Th1 cytokine, has shown paradoxical effects against diabetes. The mechanism underlying such variable function remains largely undefined. An approach for controlled mobilization of endogenous IL-10 was applied to the NOD mouse and indicated that IL-10 encounter with diabetogenic T cells within the islets sustains activation, while encounter occurring peripheral to the islets induces tolerance. Insulin beta-chain (INSbeta) 9-23 peptide was expressed on an Ig, and the aggregated (agg) form of the resulting Ig-INSbeta triggered IL-10 production by APCs, and expanded IL-10-producing T regulatory cells. Consequently, agg Ig-INSbeta delayed diabetes effectively in young NOD mice whose pathogenic T cells remain peripheral to the islets. However, agg Ig-INSbeta was unable to suppress the disease in 10-wk-old insulitis-positive animals whose diabetogenic T cells have populated the islets. This is not due to irreversibility of the disease because soluble Ig-INSbeta did delay diabetes in these older mice. Evidence is provided indicating that upon migration to the islet, T cells were activated and up-regulated CTLA-4 expression. IL-10, however, reverses such up-regulation, abolishing CTLA-4-inhibitory functions and sustaining activation of the islet T lymphocytes. Therefore, IL-10 supports T cell tolerance in the periphery, but its interplay with CTLA-4 sustains activation within the islets. As a result, IL-10 displays opposite functions against diabetes in young vs older insulitis-positive mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
174
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
662-70
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15634884-Amino Acid Sequence, pubmed-meshheading:15634884-Animals, pubmed-meshheading:15634884-Antigen-Presenting Cells, pubmed-meshheading:15634884-Antigens, CD, pubmed-meshheading:15634884-Antigens, Differentiation, pubmed-meshheading:15634884-CTLA-4 Antigen, pubmed-meshheading:15634884-Cell Differentiation, pubmed-meshheading:15634884-Diabetes Mellitus, Type 1, pubmed-meshheading:15634884-Down-Regulation, pubmed-meshheading:15634884-Female, pubmed-meshheading:15634884-Immune Tolerance, pubmed-meshheading:15634884-Immunosuppressive Agents, pubmed-meshheading:15634884-Insulin Antibodies, pubmed-meshheading:15634884-Interleukin-10, pubmed-meshheading:15634884-Islets of Langerhans, pubmed-meshheading:15634884-Lymphocyte Activation, pubmed-meshheading:15634884-Mice, pubmed-meshheading:15634884-Mice, Inbred NOD, pubmed-meshheading:15634884-Mice, Knockout, pubmed-meshheading:15634884-Mice, SCID, pubmed-meshheading:15634884-Molecular Sequence Data, pubmed-meshheading:15634884-T-Lymphocyte Subsets, pubmed-meshheading:15634884-T-Lymphocytes, Regulatory
pubmed:year
2005
pubmed:articleTitle
IL-10 diminishes CTLA-4 expression on islet-resident T cells and sustains their activation rather than tolerance.
pubmed:affiliation
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't