| First Author | Irla M | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e52591 |
| PubMed ID | 23300712 | Mgi Jnum | J:195832 |
| Mgi Id | MGI:5485338 | Doi | 10.1371/journal.pone.0052591 |
| Citation | Irla M, et al. (2012) Antigen recognition by autoreactive CD4(+) thymocytes drives homeostasis of the thymic medulla. PLoS One 7(12):e52591 |
| abstractText | 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. |
