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Il2 allelic variation in non-obese diabetic mice imparts marked resistance to type 1 diabetes. IL-2 is pivotal for the fitness and homeostasis of Foxp3++ regulatory T (Treg) cells, and the Idd3B6 locus augments IL-2 production by effector T cells, which in turn enhances the potency of Treg cell functions. Given the important role dendritic cells (DCs) play in Treg cell-mediated tolerance induction, we hypothesized that DCs from Idd3B6 congenic mice contribute to increased Treg cell activity. Here, we observed that CD11c++ DCs, harboring protective Idd3B6 genes, are endowed with the capacity to secrete IL-2, enabling them to preferentially promote Treg cell functions in vitro and in vivo. Our results show that Il2 gene variation may imprint DCs to favor T-cell regulation of autoimmunity. [ABSTRACT FROM AUTHOR]