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

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