Figure 6.

XBP-1s blockade reduces human skin graft rejection and xenogeneic GVHD. NSG mice received a 1 cm² split thickness human skin graft. After 30 days of rest to permit engraftment, 5 × 10⁶ human PBMCs (allogeneic to the skin) were injected into the mice. Unique pairs of donor skin and allogeneic PBMCs were used for each set of experiments. B-I09 30 mg/kg or vehicle was given by i.p. injection 5 days a week for 3 weeks. Mice were humanely euthanized and the skin graft, spleen, lung, and liver were harvested from the recipient on day +21 from time of PBMC injection. (A) Representative H&E sections compare skin graft rejection and xenogeneic GVHD in the liver and lung among no PBMC controls, mice that received PBMCs plus vehicle, and mice that received PBMCs plus B-I09 (100X). (B–D) Bar graphs show skin graft rejection and xenogeneic GVHD scores (blinded assessment) at day +21. (E) Representative contour plots show the amount of detectable XBP-1s in CD3 negative cells residing in the murine spleen at day +21. Pooled data from two independent experiments, up to 7 mice per group, Mann–Whitney test.