Irla M Guerri L Guenot J Sergé A Lantz O Liston A Imhof BA Palmer E Reith W 2012 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. application/pdf https://sonar.ch/global/documents/221799 eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0052591 info:eu-repo/semantics/altIdentifier/pmid/23300712 info:eu-repo/semantics/openAccess PloS one. - 2012 Animals Autoantigens Body Patterning CD4 Antigens CD40 Antigens CD40 Ligand Cell Proliferation Epithelial Cells Female Gene Expression Homeostasis Lymphotoxin beta Receptor Lymphotoxin-alpha Male Mice Mice, Inbred C57BL Mice, Knockout Receptor Activator of Nuclear Factor-kappa B Signal Transduction Thymocytes Thymus Gland Tissue Culture Techniques Antigen recognition by autoreactive CD4⁺ thymocytes drives homeostasis of the thymic medulla. http://purl.org/coar/resource_type/c_6501