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Title: Antigen recognition by autoreactive CD4⁺ thymocytes drives homeostasis of the thymic medulla
Authors: Irla, Magali ×
Guerri, Lucia
Guenot, Jeanne
Sergé, Arnauld
Lantz, Olivier
Liston, Adrian
Imhof, Beat A
Palmer, Ed
Reith, Walter #
Issue Date: 2012
Publisher: Public Library of Sciene
Series Title: PLoS One vol:7 issue:12 pages:e52591
Article number: 10.1371/journal.pone.0052591
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 α 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.
ISSN: 1932-6203
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Genetics of Autoimmunity
× corresponding author
# (joint) last author

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