Autoantigen-specific interactions with CD4(+) thymocytes control mature medullary thymic epithelial cell cellularity
- Author(s)
- Irla, M; Hugues, S; Gill, J; Nitta, T; Hikosaka, Y; Williams, IR; Hubert, FX; Scott, HS; Takahama, Y; Hollander, GA; Reith, W;
- Details
- Publication Year 2008-09-19,Volume 29,Issue #3,Page 451-463
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- 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.
- Publisher
- CELL PRESS
- Keywords
- CLASS-II TRANSACTIVATOR; PROMISCUOUS GENE-EXPRESSION; T-CELLS; SELF-TOLERANCE; IN-VIVO; POSITIVE SELECTION; DENDRITIC CELLS; DEFICIENT MICE; PROMOTER-IV; MHC
- Publisher's Version
- https://doi.org/10.1016/j.immuni.2008.08.007
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-09-19 12:00:00