Tregs mediate the GVHD-protective capacity of peri-alloHCT delivery of IL-33. (A) Foxp3-DTR B6 mice were administered 15 ng/g DT starting on day −11 (every other day) concurrently with daily IL-33 administration starting on day −10. On day −1, mice received lethal TBI (1100 cGy) followed by 1 × 107 WT BALB/c TCD-BM alone or with 2 × 106 BALB/c pan T cells on day 0. DT was continued through day +3 and IL-33 through day +4 posttransplant. (B) Resulting survival curves with statistical significances calculated by log-rank (Mantel-Cox) test (*P < .05, **P < .01, ***P < .001). (C) Recorded clinical scores are presented. Significant differences for each point with ≥3 mice were calculated between: (1) BM + T cells + IL-33 vs BM + T cells + DT/IL-33 (*P < .05) or (2) BM + T cells + DT vs BM + T cells + IL-33 (#P < .05) using an unpaired Student t test.