Article abstract
Nature Immunology 8, 931 - 941 (2007)
Published online: 12 August 2007 | doi:10.1038/ni1504
Regulatory T cells expressing interleukin 10 develop from Foxp3+ and Foxp3- precursor cells in the absence of interleukin 10
Craig L Maynard1,2, Laurie E Harrington1, Karen M Janowski1, James R Oliver1, Carlene L Zindl2, Alexander Y Rudensky3 & Casey T Weaver1
Abstract
CD4+ regulatory T cells (Treg cells) that produce interleukin 10 (IL-10) are important contributors to immune homeostasis. We generated mice with a 'dual-reporter' system of the genes encoding IL-10 and the transcription factor Foxp3 to track Treg subsets based on coordinate or differential expression of these genes. Secondary lymphoid tissues, lung and liver had enrichment of Foxp3+IL-10- Treg cells, whereas the large and small intestine had enrichment of Foxp3+IL-10+ and Foxp3-IL-10+ Treg cells, respectively. Although negative for Il10 expression, both Foxp3+ and Foxp3- CD4+ thymic precursor cells gave rise to peripheral IL-10+ Treg cells, with only Foxp3- precursor cells giving rise to all Treg subsets. Each Treg subset developed in IL-10-deficient mice, but this was blocked by treatment with antibody to transforming growth factor-
. Thus, Foxp3+ and Foxp3- precursor cells give rise to peripheral IL-10-expressing Treg cells by a mechanism dependent on transforming growth factor- and independent of IL-10.
- Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
- Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Correspondence to: Casey T Weaver1 e-mail: cweaver@uab.edu
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