Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells

Nat Immunol. 2003 Apr;4(4):330-6. doi: 10.1038/ni904. Epub 2003 Mar 3.

Abstract

CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. Here we report that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development. The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic defect of CD4+CD25- T cells. CD4+CD25+ regulatory T cells rescue disease development and preferentially expand when transferred into neonatal Foxp3-deficient mice. Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25- T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors
  • Gene Targeting
  • Mice
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Interleukin-2