Linked Life Data

21248249

Source:http://linkedlifedata.com/resource/pubmed/id/21248249

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-3
pubmed:abstractText
The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially autoaggressive CD4(+) T cells. In this study, we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme Ag expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4(+) T cells in prediabetic 3A9-TCR × insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency, because it does not affect thymic negative selection of islet-reactive CD4(+) cells or the numbers of islet-specific CD4(+) or CD4(+)Foxp3(+) T cells in the periphery, although it decreased differentiation of inducible regulatory T cells from TGF-?-treated 3A9-TCR cells in vitro. When removed from regulatory T cells and placed in culture, Cblb-deficient islet-reactive CD4(+) cells reveal a capacity to proliferate to HEL Ag that is repressed in wild-type cells. This latent failure of T cell anergy is, nevertheless, controlled in vivo in prediabetic mice so that islet-reactive CD4(+) cells in the spleen and the pancreatic lymph node of Cblb-deficient mice show no evidence of increased activation or proliferation in situ. Cblb deficiency subsequently precipitated diabetes in most TCR:insHEL animals by 15 wk of age. These results reveal a role for peripheral T cell anergy in organ-specific self-tolerance and illuminate the interplay between Cblb-dependent anergy and other mechanisms for preventing organ-specific autoimmunity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2024-32
pubmed:meshHeading
pubmed-meshheading:21248249-Adaptor Proteins, Signal Transducing, pubmed-meshheading:21248249-Animals, pubmed-meshheading:21248249-Autoantibodies, pubmed-meshheading:21248249-CD4-Positive T-Lymphocytes, pubmed-meshheading:21248249-Cells, Cultured, pubmed-meshheading:21248249-Clonal Anergy, pubmed-meshheading:21248249-Diabetes Mellitus, Type 1, pubmed-meshheading:21248249-Disease Progression, pubmed-meshheading:21248249-Forkhead Transcription Factors, pubmed-meshheading:21248249-Genetic Predisposition to Disease, pubmed-meshheading:21248249-Islets of Langerhans, pubmed-meshheading:21248249-Lymphocyte Activation, pubmed-meshheading:21248249-Mice, pubmed-meshheading:21248249-Mice, Inbred C57BL, pubmed-meshheading:21248249-Mice, Transgenic, pubmed-meshheading:21248249-Organ Specificity, pubmed-meshheading:21248249-Pancreas, pubmed-meshheading:21248249-Proto-Oncogene Proteins c-cbl, pubmed-meshheading:21248249-T-Lymphocytes, Regulatory
pubmed:year
2011
pubmed:articleTitle
Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes.
pubmed:affiliation
Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 0200, Australia. gerard.hoyne@nd.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't