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Related Experiment Videos

Foxp3 programs the development and function of CD4+CD25+ regulatory T cells.

Jason D Fontenot1, Marc A Gavin, Alexander Y Rudensky

  • 1Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195, USA.

Nature Immunology
|March 4, 2003
PubMed
Summary

The forkhead transcription factor Foxp3 is crucial for the development and function of CD4+CD25+ regulatory T cells, which suppress autoimmunity. Its absence leads to lethal autoimmune disease due to a deficiency in these regulatory T cells.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • CD4+CD25+ regulatory T cells are vital for preventing autoimmune diseases.
  • The specific molecular mechanisms governing regulatory T cell development and function remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the transcription factor Foxp3 in the development and function of CD4+CD25+ regulatory T cells.
  • To determine if Foxp3 is essential for the suppressive capacity of regulatory T cells.

Main Methods:

  • Analysis of Foxp3 expression in CD4+CD25+ regulatory T cells.
  • Phenotypic and functional characterization of T cells from Foxp3-mutant (scurfy) and Foxp3-null mice.
  • In vivo transfer experiments of CD4+CD25+ regulatory T cells into neonatal Foxp3-deficient mice.

Related Experiment Videos

  • Ectopic expression of Foxp3 in CD4+CD25- T cells.

    • Main Results:

    • Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is indispensable for their development.
    • Autoimmune disease in Foxp3-mutant mice stems from a deficiency in CD4+CD25+ regulatory T cells, not intrinsic T cell defects.
    • Transfer of CD4+CD25+ regulatory T cells ameliorates disease in Foxp3-deficient recipients.
    • Forced expression of Foxp3 imparts suppressor function to conventional CD4+CD25- T cells.

    Conclusions:

    • Foxp3 is a critical determinant of CD4+CD25+ regulatory T cell development and function.
    • Foxp3 acts as a master regulator, essential for maintaining immune tolerance and preventing autoimmunity.