Scientific article
Open access

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

Published inPloS one, vol. 7, no. 12, e52591
Publication date2012

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.

  • Animals
  • Antigens, CD4/metabolism
  • Antigens, CD40/metabolism
  • Autoantigens/immunology
  • Body Patterning
  • CD40 Ligand/metabolism
  • Cell Proliferation
  • Epithelial Cells/metabolism/physiology
  • Female
  • Gene Expression
  • Homeostasis
  • Lymphotoxin beta Receptor/metabolism
  • Lymphotoxin-alpha/genetics/metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor Activator of Nuclear Factor-kappa B/metabolism
  • Signal Transduction
  • Thymocytes/immunology/metabolism/physiology
  • Thymus Gland/cytology/growth & development/immunology
  • Tissue Culture Techniques
Citation (ISO format)
IRLA, Magali et al. Antigen recognition by autoreactive CD4⁺ thymocytes drives homeostasis of the thymic medulla. In: PloS one, 2012, vol. 7, n° 12, p. e52591. doi: 10.1371/journal.pone.0052591
Main files (1)
Article (Published version)
ISSN of the journal1932-6203

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