Low dose interleukin-2 (LDIL-2) can effectively expand endogenous circulating regulatory T-cells (Tregs) in vivo, but its role in promoting allograft tolerance in humans has not been investigated. We conducted a clinical trial in stable liver transplant recipients to determine the capacity of LDIL-2 to suppress allospecific immune responses and allow the complete discontinuation of maintenance immunosuppression (clinicaltrials.gov NCT02949492). LDIL-2 treatment achieved a marked and sustained increase in circulating Tregs in all patients. However, this was not associated with the preferential expansion of donor-reactive Tregs, did not promote the accumulation of Tregs within the liver allograft, failed to induce tolerance and primed the allograft for rejection even before immunosuppression weaning was initiated. Overall design: PBMC and Liver biopsies were extracted from six subjects treated with LDIL-2 at baseline and four weeks.