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

CD4 + regulatory T cells (T reg 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 T reg subsets based on coordinate or differential expression of these genes. Secondary lymphoid tissues, lung and liver had enrichment of Foxp3 + IL-10 − T reg cells, whereas the large and small intestine had enrichment of Foxp3 + IL-10 + and Foxp3 − IL-10 + T reg cells, respectively. Although negative for Il10 expression, both Foxp3 + and Foxp3 − CD4 + thymic precursor cells gave rise to peripheral IL-10 + T reg cells, with only Foxp3 − precursor cells giving rise to all T reg subsets. Each T reg subset developed in IL-10-deficient mice, but this was blocked by treatment with antibody to transforming growth factor-β. Thus, Foxp3 + and Foxp3 − precursor cells give rise to peripheral IL-10-expressing T reg cells by a mechanism dependent on transforming growth factor-β and independent of IL-10.