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

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 (T(reg)). 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(+) T(reg) 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 contrib

SUBMITTER: Komatsu N 

PROVIDER: S-EPMC1885610 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature