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https://hdl.handle.net/2440/52555
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Type: | Journal article |
Title: | Autoantigen-specific interactions with CD4(+) thymocytes control mature medullary thymic epithelial cell cellularity |
Author: | Irla, M. Hugues, S. Gill, J. Nitta, T. Hikosaka, Y. Williams, I. Hubert, F. Scott, H. Takahama, Y. Hollander, G. Reith, W. |
Citation: | Immunity, 2008; 29(3):451-463 |
Publisher: | Cell Press |
Issue Date: | 2008 |
ISSN: | 1074-7613 1097-4180 |
Statement of Responsibility: | Magali Irla, Stéphanie Hugues, Jason Gill, Takeshi Nitta, Yu Hikosaka, Ifor R. Williams, François-Xavier Hubert, Hamish S. Scott, Yousuke Takahama, Georg A. Holländer and Walter Reith |
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. |
Keywords: | Thymus Gland CD4-Positive T-Lymphocytes Epithelial Cells Animals Mice, Knockout Humans Mice Trans-Activators CD40 Ligand Nuclear Proteins Transcription Factors Autoantigens Self Tolerance CD40 Antigens |
Description: | Copyright © 2008 Elsevier Inc. |
DOI: | 10.1016/j.immuni.2008.08.007 |
Description (link): | http://www.cell.com/immunity/home |
Published version: | http://dx.doi.org/10.1016/j.immuni.2008.08.007 |
Appears in Collections: | Aurora harvest Medicine publications |
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