Control of regulatory T cell development by the transcription factor Foxp3

Science. 2003 Feb 14;299(5609):1057-61. doi: 10.1126/science.1079490. Epub 2003 Jan 9.

Abstract

Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / analysis
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / prevention & control
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Forkhead Transcription Factors
  • Gastritis / immunology
  • Gastritis / prevention & control
  • Immune Tolerance*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / prevention & control
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mice, Transgenic
  • Mutation
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / analysis
  • Recombinant Fusion Proteins / metabolism
  • Self Tolerance
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Transduction, Genetic

Substances

  • Antigens, CD
  • Cytokines
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins