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

Journal article

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.

Authors: Irla, M; Hugues, S; Gill, J; Nitta, T; Hikosaka, Y

• Publication status: Published
• Journal: Immunity
• Volume: 29
• Issue: 3
• Pages: 451-463
• Publication date: 2008-09-01
• DOI: 10.1016/j.immuni.2008.08.007
• EISSN: 1097-4180
• ISSN: 1074-7613
• Language: English
• Keywords: Nuclear Proteins; Autoantigens; Mice, Knockout; CD4-Positive T-Lymphocytes; Animals; CD40 Ligand; Thymus Gland; Self Tolerance; Mice; Antigens, CD40; Epithelial Cells; Humans; Trans-Activators; Transcription Factors