Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter

Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5126-31. doi: 10.1073/pnas.0501701102. Epub 2005 Mar 28.

Abstract

Regulatory T cells are critical for maintaining self-tolerance and to negatively regulate immune responses. Foxp3 is a regulatory T cell-specific transcription factor that functions as the master regulator of the development and function of regulatory T cells. Here, we report the generation of a mouse model, in which a bicistronic reporter expressing a red fluorescent protein has been knocked into the endogenous Foxp3 locus. Using this mouse model, we assessed Foxp3 expression in various lymphocyte compartments and identified previously unreported Foxp3-expressing cells. In addition, we showed that de novo Foxp3 expression along with suppressive function were induced by TGF-beta in activated CD4 T cells in vitro. Finally, we demonstrated that non-Foxp3-expressing CD4 T cells could not be converted into Foxp3-expressing cells upon adoptive transfer into immunodeficient hosts. This Foxp3 bicistronic reporter knockin mouse model should greatly enhance the study of regulation and function of Foxp3-expressing regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Base Sequence
  • DNA / genetics
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Forkhead Transcription Factors
  • Gene Expression
  • Genes, Reporter
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Animal
  • Models, Immunological
  • Recombinant Proteins / genetics
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / immunology
  • Severe Combined Immunodeficiency / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Luminescent Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • red fluorescent protein
  • DNA