UNIGE document Scientific Article
previous document  unige:1443  next document
add to browser collection
Title

Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity

Authors
Gill, Jason
Nitta, Takeshi
Hikosaka, Yu
Williams, Ifor R.
Hubert, François-Xavier
show hidden authors show all authors [1 - 11]
Published in Immunity. 2008, vol. 29, no. 3, p. 451-63
Abstract 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.
Keywords AnimalsAntigens, CD40/immunology/metabolismAutoantigens/immunologyCD4-Positive T-Lymphocytes/cytology/immunology/metabolismCD40 Ligand/immunology/metabolismEpithelial Cells/cytology/immunology/metabolismHumansMiceMice, KnockoutNuclear Proteins/immunology/metabolismSelf ToleranceThymus Gland/cytology/immunology/metabolismTrans-Activators/immunology/metabolismTranscription Factors/immunology/metabolism
Stable URL http://archive-ouverte.unige.ch/unige:1443
Full text
Article (Author postprint) (2.6 MB) - document accessible for UNIGE members only Limited access to UNIGE
Supplemental data - I (1.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Supplemental data - II (230 Kb) - public document Free access
Supplemental data - III (201 Kb) - public document Free access
Identifiers
PMID: 18799151
Structures
Research groups Groupe Reith Walter (pathologie et immunologie) (282)
Pathologie et immunologie (906)

128 hits

61 downloads

Update

Deposited on : 2009-04-28

Export document
Format :
Citation style :