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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-9-18
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pubmed:abstractText |
Medullary thymic epithelial cells (mTECs) are specialized for inducing central immunological tolerance to self-antigens. To accomplish this, mTECs must adopt a mature phenotype characterized by expression of the autoimmune regulator Aire, which activates the transcription of numerous genes encoding tissue-restricted self-antigens. The mechanisms that control mature Aire(+) mTEC development in the postnatal thymus remain poorly understood. We demonstrate here that, although either CD4(+) or CD8(+) thymocytes are sufficient to sustain formation of a well-defined medulla, expansion of the mature mTEC population requires autoantigen-specific interactions between positively selected CD4(+) thymocytes bearing autoreactive T cell receptor (TCR) and mTECs displaying cognate self-peptide-MHC class II complexes. These interactions also involve the engagement of CD40 on mTECs by CD40L induced on the positively selected CD4(+) thymocytes. This antigen-specific TCR-MHC class II-mediated crosstalk between CD4(+) thymocytes and mTECs defines a unique checkpoint in thymic stromal development that is pivotal for generating a mature mTEC population competent for ensuring central T cell tolerance.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1097-4180
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pubmed:author |
pubmed-author:GillJasonJ,
pubmed-author:HikosakaYuY,
pubmed-author:HolländerGeorg AGA,
pubmed-author:HubertFrançois-XavierFX,
pubmed-author:HuguesStéphanieS,
pubmed-author:IrlaMagaliM,
pubmed-author:NittaTakeshiT,
pubmed-author:ReithWalterW,
pubmed-author:ScottHamish SHS,
pubmed-author:TakahamaYousukeY,
pubmed-author:WilliamsIfor RIR
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
451-63
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pubmed:dateRevised |
2009-6-8
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pubmed:meshHeading |
pubmed-meshheading:18799151-Animals,
pubmed-meshheading:18799151-Antigens, CD40,
pubmed-meshheading:18799151-Autoantigens,
pubmed-meshheading:18799151-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18799151-CD40 Ligand,
pubmed-meshheading:18799151-Epithelial Cells,
pubmed-meshheading:18799151-Humans,
pubmed-meshheading:18799151-Mice,
pubmed-meshheading:18799151-Mice, Knockout,
pubmed-meshheading:18799151-Nuclear Proteins,
pubmed-meshheading:18799151-Self Tolerance,
pubmed-meshheading:18799151-Thymus Gland,
pubmed-meshheading:18799151-Trans-Activators,
pubmed-meshheading:18799151-Transcription Factors
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pubmed:year |
2008
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pubmed:articleTitle |
Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity.
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pubmed:affiliation |
University of Geneva Medical School, CMU, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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