Foxp3+ regulatory T cells promiscuously accept thymic signals critical for their development

Philip J Spence, E Allison Green

Research output: Contribution to journalArticlepeer-review

Abstract

Foxp3(+) regulatory T cells develop in the thymus and are essential for maintaining peripheral tolerance to self tissues. We report the critical requirement for CD154 up-regulation specifically on, and during the thymic development of, Foxp3(+) regulatory T cells for the induction of their clonal expansion within the medulla. In the absence of this signal, there was a severe reduction in their thymic generation and output, leading to decreased peripheral numbers. Importantly, CD40 expression on either thymic dendritic or epithelial cells was sufficient to promote the development of normal numbers of Foxp3(+) regulatory T cells. This work suggests that CD154-transduced signals promote Foxp3(+) regulatory T cell development and highlights the plasticity of the thymic stroma for supporting their generation. Crucially, this study demonstrates that Foxp3(+) regulatory T cells can promiscuously accept a single critical signal necessary for their thymic development from different cellular sources, redefining our understanding of their generation.
Original languageEnglish
Pages (from-to)973-978
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number3
DOIs
Publication statusPublished - 22 Jan 2008

Keywords

  • Animals
  • Antigen Presentation
  • Antigens, CD28
  • Antigens, CD40
  • Antigens, CD80
  • Antigens, CD86
  • CD40 Ligand
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells
  • Epithelial Cells
  • Female
  • Forkhead Transcription Factors
  • Male
  • Mice
  • Mice, Knockout
  • Signal Transduction
  • T-Lymphocytes, Regulatory
  • Thymus Gland

Cite this