The Journal of Experimental Medicine
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Published online January 2, 2007
doi:10.1084/jem.20061852
The Journal of Experimental Medicine, Vol. 204, No. 1, 57-63
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Lahl et al.
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BRIEF DEFINITIVE REPORT

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

Katharina Lahl1, Christoph Loddenkemper2, Cathy Drouin1, Jennifer Freyer3, Jon Arnason1, Gérard Eberl4, Alf Hamann3, Hermann Wagner1, Jochen Huehn3, and Tim Sparwasser1

1 Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany
2 Institut für Pathologie, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany
3 Experimentelle Rheumatologie, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité Universitätsmedizin Berlin, Campus Mitte, 10117 Berlin, Germany
4 Laboratory of Lymphoid Tissue Development, Institut Pasteur, 75724 Paris, France

CORRESPONDENCE Tim Sparwasser: tim.sparwasser{at}lrz.tum.de

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.

J. Huehn and T. Sparwasser contributed equally to this work.


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