Autoantigen-specific interactions with CD4+ thymocytes control mature medullary thymic epithelial cell cellularity
| Autor: | Magali Irla, Yu Hikosaka, Stéphanie Hugues, Jason Gill, Hamish S. Scott, Walter Reith, Georg A. Holländer, Takeshi Nitta, Yousuke Takahama, Ifor R. Williams, François-Xavier Hubert |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Stromal cell
Epithelial Cells/cytology/immunology/metabolism T cell Immunology Population ddc:616.07 Mice 03 medical and health sciences 0302 clinical medicine Autoantigens/immunology CD4-Positive T-Lymphocytes/cytology/immunology/metabolism medicine Animals Humans Immunology and Allergy education Transcription factor 030304 developmental biology Mice Knockout 0303 health sciences education.field_of_study CD40 biology Thymus Gland/cytology/immunology/metabolism Trans-Activators/immunology/metabolism Transcription Factors/immunology/metabolism T-cell receptor Autoimmune regulator Cell biology Antigens CD40/immunology/metabolism Self Tolerance Infectious Diseases medicine.anatomical_structure CELLIMMUNO biology.protein Nuclear Proteins/immunology/metabolism CD40 Ligand/immunology/metabolism CD8 030215 immunology |
| Zdroj: | Immunity, Vol. 29, No 3 (2008) pp. 451-63 Publons |
| ISSN: | 1074-7613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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