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Juicing Tregs in situ to improve kidney allograft outcomes. Targeted deletion of the sirtuin-1, Sirt-1, gene in mouse T cells results in enhanced CD4(+) T regulatory cell function. When these mice are used as kidney allograft recipients, this deletion confers marked improvements in allograft function and survival with the development of donor-specific nonresponsiveness. Similar kidney allograft outcomes are produced in wild-type recipients treated with pharmacologic Sirt-1 inhibitors. These studies suggest a novel strategy for enhancing the immunosuppressive function of Tregs to improve graft outcomes in kidney transplant patients.