Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells

Immunity. 2006 Aug;25(2):249-59. doi: 10.1016/j.immuni.2006.05.016. Epub 2006 Aug 3.

Abstract

Foxp3(+)CD4(+)CD25(+) regulatory T cells can differentiate from Foxp3(-)CD4(+) medullary thymocytes and Foxp3(-)CD4(+) naive T cells. However, the impact of these two processes on size and composition of the peripheral repertoire of regulatory T cells is unclear. Here we followed the fate of individual Foxp3(+)CD4(+)CD25(+) thymocytes and T cells in vivo in T cell receptor (TCR) transgenic mice that express a restricted but polyclonal repertoire of TCRs. By utilizing high-throughput single-cell analysis, we showed that Foxp3(+)CD4(+) peripheral T cells were derived from thymic precursors that expressed a different TCRs than Foxp3(-)CD4(+) medullary thymocytes and Foxp3(-)CD4(+) T cells. Furthermore, the diversity of TCRs on Foxp3(+)CD4(+) regulatory T cells exceeded the diversity of TCRs on Foxp3(-)CD4(+) naive T cells, even in mice that lack expression of tissue-specific antigens. Our results imply that higher TCR diversity on Foxp3(+) regulatory T cells helps these cells to match the specificities of autoreactive and naive T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Differentiation
  • Cell Lineage*
  • Cells, Cultured
  • Forkhead Transcription Factors / chemistry
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism*
  • Mice
  • Molecular Sequence Data
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Autoantigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Peptides
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2