Regulatory T cells expressing interleukin 10 develop from Foxp3 + and Foxp3 - precursor cells in the absence

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