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Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease.

The scurfy mutant mouse strain suffers from a fatal lymphoproliferative disease leading to early death within 3-4 wk of age. A frame-shift mutation of the forkhead box transcription factor Foxp3 has been identified as the molecular cause of this multiorgan autoimmune disease. Foxp3 is a central control element in the development and function of regulatory T cells (T reg cells), which are necessary for the maintenance of self-tolerance. However, it is unclear whether dysfunction or a lack of T reg cells is etiologically involved in scurfy pathogenesis and its human correlate, the IPEX syndrome. We describe the generation of bacterial artificial chromosome-transgenic mice termed "depletion of regulatory T cell" (DEREG) mice expressing a diphtheria toxin (DT) receptor-enhanced green fluorescent protein fusion protein under the control of the foxp3 gene locus, allowing selective and efficient depletion of Foxp3+ T reg cells by DT injection. Ablation of Foxp3+ T reg cells in newborn DEREG mice led to the development of scurfy-like symptoms with splenomegaly, lymphadenopathy, insulitis, and severe skin inflammation. Thus, these data provide experimental evidence that the absence of Foxp3+ T reg cells is indeed sufficient to induce a scurfy-like phenotype. Furthermore, DEREG mice will allow a more precise definition of the function of Foxp3+ T reg cells in immune reactions in vivo.

Pubmed ID: 17200412

Authors

  • Lahl K
  • Loddenkemper C
  • Drouin C
  • Freyer J
  • Arnason J
  • Eberl G
  • Hamann A
  • Wagner H
  • Huehn J
  • Sparwasser T

Journal

The Journal of experimental medicine

Publication Data

January 22, 2007

Associated Grants

None

Mesh Terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Chromosomes, Artificial, Bacterial
  • DNA Primers
  • Diphtheria Toxin
  • Forkhead Transcription Factors
  • Green Fluorescent Proteins
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Lymphoproliferative Disorders
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Phenotype
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • T-Lymphocytes, Regulatory