NDLI: Full restoration of peripheral Foxp3+ regulatory T cell pool by radioresistant host cells in scurfy bone marrow chimeras

Content Provider	PubMed Central
Author	Komatsu, Noriko Hori, Shohei
Copyright Year	2007
Abstract	Mutations in the gene encoding the transcription factor Foxp3 lead to fatal autoimmune pathology in mice and humans, which is associated with a deficiency in Foxp3+ regulatory T cells (Treg). It has also been proposed that Foxp3 inactivation in nonhematopoietic tissues, particularly in thymic epithelium, is required for the pathogenesis, because Foxp3 mutant scurfy bone marrow cells fail to transmit the disease to lethally irradiated WT hosts. We demonstrate here that the lack of pathology in these radiation chimeras is due to the presence of radioresistant endogenous Foxp3+ Treg of the host. In addition, chimeras carrying the scurfy mutation only in nonhematopoietic cells exhibit no evidence of autoimmune pathology. Thus, Foxp3 deficiency in nonhematopoietic cells does not contribute to the scurfy disease. Furthermore, our analyses of radiation chimeras revealed that the peripheral Treg pool is fully and specifically restored and maintained by radioresistant endogenous Treg or adoptively transferred exogenous Treg through “homeostatic” proliferation in the absence of Treg production from scurfy donor bone marrow cells. These results thus provide evidence that the autoimmune pathology in scurfy mice results indeed from a Treg deficiency and illustrate a robust homeostatic mechanism that strictly controls the size of peripheral Treg pool by fine-tuning of homeostatic proliferation.
Related Links	http://dx.doi.org/10.1073/pnas.0702004104
Ending Page	8964
Page Count	6
Starting Page	8959
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	21
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-05-22
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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