Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells

J Immunol Methods. 2007 Jan 30;319(1-2):41-52. doi: 10.1016/j.jim.2006.10.008. Epub 2006 Nov 3.


Although quantitative identification and viable enrichment of natural regulatory T cells (T-regs) in humans are problematic, such steps would greatly facilitate the analysis of these cells in disease states. In an attempt to identify markers that are sensitive and specific for human T-regs, we analyzed the expression of fourteen intracellular and cell surface markers on human CD4(+) cells. Many markers were partially selective for CD25(hi) T-regs, but consistent and specific discrimination of functional T-regs was only made possible by focus on CD127, the alpha chain of the IL-7 receptor. Although most CD4(+) human T cells express CD127, T-regs exhibiting suppressive activity in vitro display distinctly lower surface expression of this marker, irrespective of their level of CD25 expression. Sorted cells with the surface phenotype CD4(+)CD25(+)CD127(low) had higher levels of intracellular FOXP3 and CTLA-4 and, as determined by functional assays, were suppressive, hypoproliferative, and poorly responsive to TCR signaling. The CD4(+)CD25(+)CD127(low) phenotype was also found to be characteristic of T-regs found in mice and in rhesus macaques. This surface phenotype should allow for quantitative studies of regulatory T cells in disease states as well as for enrichment of live regulatory T cells for functional analyses and/or expansion in vitro.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Biomarkers / metabolism
  • Cell Separation*
  • Cell Survival / immunology
  • Female
  • Flow Cytometry*
  • Humans
  • Interleukin-7 Receptor alpha Subunit / biosynthesis*
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Lymphocyte Activation / immunology
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • T-Lymphocytes, Regulatory / metabolism*


  • Biomarkers
  • Interleukin-7 Receptor alpha Subunit