Linked Life Data

12444169

Source:http://linkedlifedata.com/resource/pubmed/id/12444169

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-11-21
pubmed:abstractText
Because it is one of the few autoimmune disorders in which the target autoantigen has been definitively identified, myasthenia gravis (MG) provides a unique opportunity for testing basic concepts of immune tolerance. In most MG patients, Abs against the acetylcholine receptors (AChR) at the neuromuscular junction can be readily identified and have been directly shown to cause muscle weakness. T cells have also been implicated and appear to play a role in regulating the pathogenic B cells. A murine MG model, generated by immunizing mice with heterologous AChR from the electric fish Torpedo californica, has been used extensively. In these animals, Abs cross-react with murine AChR; however, the T cells do not. Thus, to study tolerance to AChR, a transgenic mouse model was generated in which the immunodominant Torpedo AChR (T-AChR) alpha subunit is expressed in appropriate tissues. Upon immunization, these mice showed greatly reduced T cell responses to T-AChR and the immunodominant alpha-chain peptide. Limiting dilution assays suggest the likely mechanism of tolerance is deletion or anergy. Despite this tolerance, immunization with intact T-AChR induced anti-AChR Abs, including Abs against the alpha subunit, and the incidence of MG-like symptoms was similar to that of wild-type animals. Furthermore, evidence suggests that this B cell response to the alpha-chain receives help from T cells directed against the other AChR polypeptides (beta, gamma, or delta). This model offers a novel opportunity to elucidate mechanisms of tolerance regulation to muscle AChR and to clarify the role of T cells in MG.
pubmed:grant
pubmed:language
eng
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6570-9
pubmed:dateRevised
2007-11-14
pubmed:articleTitle
Split tolerance in a novel transgenic model of autoimmune myasthenia gravis.
pubmed:affiliation
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78229, USA.