Phenotypic and functional properties of Helios+ regulatory T cells

PLoS One. 2012;7(3):e34547. doi: 10.1371/journal.pone.0034547. Epub 2012 Mar 30.


Helios, an Ikaros family transcription factor, is preferentially expressed at the mRNA and protein level in regulatory T cells. Helios expression previously appeared to be restricted to thymic-derived Treg. Consistent with recent data, we show here that Helios expression is inducible in vitro under certain conditions. To understand phenotypic and functional differences between Helios(+) and Helios(-) Treg, we profiled cell-surface markers of FoxP3(+) Treg using unmanipulated splenocytes. We found that CD103 and GITR are expressed at high levels on a subset of Helios(+) Treg and that a Helios(+) Treg population could be significantly enriched by FACS sorting using these two markers. Quantitative real-time PCR (qPCR) analysis revealed increased TGF-β message in Helios(+) Treg, consistent with the possibility that this population possesses enhanced regulatory potential. In tumor-bearing mice, we found that Helios(+) Treg were relatively over-represented in the tumor-mass, and BrdU studies showed that, in vivo, Helios(+) Treg proliferated more than Helios(-) Treg. We hypothesized that Helios-enriched Treg might exert increased suppressive effects. Using in vitro suppression assays, we show that Treg function correlates with the absolute number of Helios(+) cells in culture. Taken together, these data show that Helios(+) Treg represent a functional subset with associated CD103 and GITR expression.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic
  • Glucocorticoid-Induced TNFR-Related Protein / genetics
  • Integrin alpha Chains / genetics
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / genetics
  • Phenotype
  • Spleen / cytology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transcription Factors / genetics*
  • Up-Regulation


  • Antigens, CD
  • DNA-Binding Proteins
  • Glucocorticoid-Induced TNFR-Related Protein
  • Integrin alpha Chains
  • Tnfrsf18 protein, mouse
  • Transcription Factors
  • Zfpn1a2 protein, mouse
  • alpha E integrins