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-β. Thus, Foxp3+ and Foxp3β precursor cells give rise to peripheral IL-10-expressing Treg cells by a mechanism dependent on transforming growth factor-β and independent of IL-10.
