Regulatory T Cell Lineage Commitment in the Thymus

Semin Immunol. 2011 Dec;23(6):401-9. doi: 10.1016/j.smim.2011.06.003. Epub 2011 Jul 6.


A substantial fraction of the Foxp3(+) CD4(+) regulatory T (T(reg)) cell repertoire is generated through instructive and/or selective processes in the thymus, and there is some consensus that clonal deviation into the T(reg) lineage is a result of self-antigen recognition. Paradoxically, the same holds true for a diametrically different cell fate decision of developing thymocytes, namely their removal from the repertoire through apoptotic cell death (clonal deletion). Here, we will review our current understanding of how T cell receptor stimulation, cytokine signaling, co-stimulation, epigenetic modifications and T cell intrinsic developmental tuning synergize during T(reg) cell differentiation, and how instructive signals converge at the Foxp3 gene-locus during entry into the T(reg) cell lineage. We will also discuss how these parameters relate to known determinants of negative selection.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Cell Differentiation
  • Cell Lineage*
  • Epigenesis, Genetic
  • Humans
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*