Antigen Recognition by Autoreactive CD4(+) Thymocytes Drives Homeostasis of the Thymic Medulla

作者：Irla Magali^*; Guerri Lucia; Guenot Jeanne; Serge Arnauld; Lantz Olivier; Liston Adrian; Imhof Beat A; Palmer Ed; Reith Walter

来源：PLos One, 2012, 7(12): e52591.

DOI：10.1371/journal.pone.0052591

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.

• 出版日期2012-12-27