The IAP inhibitor AT-406, an SMAC mimetic, exacerbates GVHD. (A) Survival. BALB/c animals received 8.5 Gy on day −1 and received transplants of 0.5 × 10⁶ CD90.2⁺ splenic T cells along with 5 × 10⁶ TCD-BM cells from either syngeneic BALB/c or allogeneic MHC-mismatched B6 donors. Recipient animals received either AT-406 (10 mg/kg) or its diluent subcutaneously on days −1, +1, +3, +5, and +7 after BMT; n = 6-21 per group). Pooled data from 4 independent experiments are shown. **P < .01, when allogeneic treated and control animals are compared. (B) Survival. B6D2F1 animals received 11 Gy on day −1 and received transplants of 3 × 10⁶ CD90.2⁺ splenic T cells along with 5 × 10⁶ TCD-BM cells from either syngeneic B6D2F1 or allogeneic MHC-mismatched haploidentical B6 donors. Recipient animals received either AT-406 (10 mg/kg) or its diluent subcutaneously on days −1, +1, +3, +5, and +7 after BMT (n = 6-30 per group). Pooled data from 6 independent experiments are shown. *P < .05, when allogeneic treated and control animals are compared. (C-E) Expansion of donor T cells (H-2k^b+CD4⁺CD8⁺) (C), CD44⁺CD62L⁻ effector T cells (D), and IFN-γ–producing T cells (E) in the spleen on day 6 after allo-BMT (n = 4-5 per group, pooled from 2 experiments). The bar shows the mean ± SEM. (F-H) The representative figures of small (F) and large intestines (G) (original magnification ×200; hematoxylin and eosin stain) and GVHD histopathological score of GI tract (small and large intestines) (H) on day 6 after allo-BMT (n = 6-10 per group, pooled from 3 experiments). *P < .05. The bar shows the mean ± SEM.