Foxp3 and natural regulatory T cells: key to a cell lineage?

Fred Ramsdell1

  • 1Celltech R&D, Inc., 1631 220th St. SE, Bothell, Washington 98021, USA. fred.ramsdell@celltechgroup.com

Immunity
|August 23, 2003
PubMed

Insights

Regulatory T (TR) cells, once called suppressor T cells, are a key focus in immunology. Research on a mutant mouse strain identified the Foxp3 gene

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • The study of suppressor T cells, now known as regulatory T (TR) cells, was largely abandoned after initial research in the 1970s.
  • Recent publications have revived interest in the critical role of TR cells in immune system regulation.
  • A mutant mouse strain, initially created for radiation studies, provides a model for understanding TR cell development.

Purpose of the Study:

  • To investigate the genetic basis of a defect in a long-established mutant mouse strain.
  • To elucidate the molecular mechanisms underlying the development and function of regulatory T (TR) cells.
  • To reconnect historical research on suppressor T cells with current understanding of TR cell biology.

Main Methods:

  • Characterization of a mutant mouse strain.
  • Genetic analysis to identify the causative gene for the observed defect.
  • Functional studies to assess the role of the identified gene in TR cell generation.

Main Results:

  • The transcription factor Foxp3 was identified as the gene responsible for the defect in scurfy mice.
  • Demonstration that Foxp3 is critical for the generation of regulatory T (TR) cells.
  • This finding provides molecular insight into the essential lineage of TR cells.

Conclusions:

  • The identification of Foxp3 as the key gene in scurfy mice offers a molecular explanation for TR cell defects.
  • This research revitalizes the study of TR cells by linking a historical model to a critical developmental gene.
  • Understanding Foxp3's role is crucial for dissecting the biology of this essential immune cell type.

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