Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells

J Immunol. 2010 Apr 1;184(7):3433-41. doi: 10.4049/jimmunol.0904028. Epub 2010 Feb 24.

Abstract

Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4(+)CD8(-)Foxp3(+) thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation ( approximately 70%) of Foxp3(+) T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-beta expressed Helios. Ag-specific Foxp3(+) T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Lineage
  • Cell Separation
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / immunology
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Ikaros Transcription Factor / biosynthesis*
  • Ikaros Transcription Factor / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Transcription Factors / biosynthesis
  • Transcription Factors / immunology

Substances

  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • IKZF2 protein, human
  • Transcription Factors
  • Zfpn1a2 protein, mouse
  • Ikaros Transcription Factor