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Antigen recognition by autoreactive CD4(+) thymocytes drives homeostasis of the thymic medulla

Irla, M. and Guerri, L. and Guenot, J. and Serge, A. and Lantz, O. and Liston, A. and Imhof, B. A. and Palmer, E. and Reith, W.. (2012) Antigen recognition by autoreactive CD4(+) thymocytes drives homeostasis of the thymic medulla. PLoS ONE, Vol. 7, H. 12 , e52591.

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Official URL: http://edoc.unibas.ch/dok/A6338223

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Abstract

The thymic medulla is dedicated for purging the T-cell receptor (TCR) repertoire of self-reactive specificities. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process because they express numerous peripheral tissue-restricted self-antigens. Although it is well known that medulla formation depends on the development of single-positive (SP) thymocytes, the mechanisms underlying this requirement are incompletely understood. We demonstrate here that conventional SP CD4(+) thymocytes bearing autoreactive TCRs drive a homeostatic process that fine-tunes medullary plasticity in adult mice by governing the expansion and patterning of the medulla. This process exhibits strict dependence on TCR-reactivity with self-antigens expressed by mTECs, as well as engagement of the CD28-CD80/CD86 costimulatory axis. These interactions induce the expression of lymphotoxin alpha in autoreactive CD4(+) thymocytes and RANK in mTECs. Lymphotoxin in turn drives mTEC development in synergy with RANKL and CD40L. Our results show that Ag-dependent interactions between autoreactive CD4(+) thymocytes and mTECs fine-tune homeostasis of the medulla by completing the signaling axes implicated in mTEC expansion and medullary organization.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Transplantation Immunology and Nephrology (Palmer/Steiger)
UniBasel Contributors:Palmer, Ed
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:10 Apr 2015 09:14

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