Prevention of GVHD by tolerogenic anti–IL-2 mAb (JES6-1A12) but not non-tolerogenic anti–IL-2 mAb (S4B6) is associated with tissue PD-L1–dependent depletion of GM-CSF–producing Th1 and Tc1 cells. Lethally irradiated WT and PD-L1^−/− BALB/c recipients were given splenocytes (2.5 × 10⁶) and TCD-BM cells (2.5 × 10⁶) from C57BL/6 donors. Recipients were given a total of 3 i.p. injections of rat-IgG, anti–IL-2 mAb (JES6-1A12), or anti–IL-2 mAb (S4B6) (500 µg/mouse) at days 0, 2, and 4 after HCT. On day 6, donor cells in the spleen, liver, and colon were analyzed for cytokine profile. (A-B) Percentage and yield of GM-CSF⁺ cells among donor IFN-γ⁺ CD4⁺ and CD8⁺ T cells in spleen, liver, and colon of WT recipients treated with anti–IL-2 mAb (JES6-1A12 or S4B6) or control IgG. (C) Percentage and yield of GM-CSF⁺ cells among donor IFN-γ⁺ CD4⁺ and CD8⁺ T cells in spleen, liver, and colon of PD-L1^−/− recipients treated with anti–IL-2 mAb (JES6-1A12) or control IgG; n = 4 per group. (D) Percentage and yield of GM-CSF⁺ cells among donor IFN-γ⁺ CD4⁺ and CD8⁺ T cells in spleen, liver, and colon of WT or PD-L1^−/− recipients treated with anti–IL-2 mAb (JES6-1A12); n = 5 per group. Data represent mean ± standard error combined from 2 replicate experiments. P values were calculated by using unpaired two-tailed Student t tests. *P < .05, **P < .01, ***P < .001, ****P < .0001.