Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. - Archive ouverte HAL Access content directly
Journal Articles Journal of Experimental Medicine Year : 2007

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

Abstract

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.
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pasteur-00161238 , version 1 (27-02-2010)

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Katharina Lahl, Christoph Loddenkemper, Cathy Drouin, Jennifer Freyer, Jon Arnason, et al.. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease.. Journal of Experimental Medicine, 2007, 204 (1), pp.57-63. ⟨10.1084/jem.20061852⟩. ⟨pasteur-00161238⟩
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