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

M Irla, S Hugues, J Gill, T Nitta, Y Hikosaka, IR Williams… - Immunity, 2008 - cell.com
M Irla, S Hugues, J Gill, T Nitta, Y Hikosaka, IR Williams, FX Hubert, HS Scott, Y Takahama
Immunity, 2008cell.com
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 …
Summary
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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