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

Irla, M. and Hugues, S. and Gill, J. and Nitta, T. and Hikosaka, Y. and Williams, I. R. and Hubert, F. X. and Scott, H. S. and Takahama, Y. and Holländer, G. A. and Reith, W.. (2008) Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity. Immunity, Vol. 29, H. 3. pp. 451-463.

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Official URL: http://edoc.unibas.ch/dok/A6005527

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Pediatric Immunology (Holländer)
UniBasel Contributors:Holländer, Georg
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1074-7613
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Apr 2014 08:00
Deposited On:25 Apr 2014 08:00

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