IAPs are not required in donor T cells to modulate GVH responses. (A-B) BALB/c animals received 8.5 Gy on day −1 and received transplants of 0.5 × 106 CD90.2+ splenic T cells from either syngeneic BALB/c or allogeneic MHC-mismatched B6-WT, B6-cIAP1−/−, or B6-XIAP−/− animals along with 5 × 106 TCD-BM cells from either syngeneic BALB/c or allogeneic B6 donors. Survival (A) and GVHD clinical score (B) (n = 11-29 per group). Pooled data from 4 independent experiments are shown. (C) B6D2F1-recipient animals received 11 Gy on day −1 and received transplants of 3 × 106 CD90.2+ splenic T cells from either syngeneic B6D2F1 or haploidentical MHC-mismatched B6-WT, B6-cIAP1−/−, or B6-XIAP−/− animals along with 5 × 106 TCD-BM cells from either syngeneic B6D2F1 or allogenic B6 donors. Survival (n = 5-11 per group). Pooled data from 2 independent experiments are shown. (D-F) Expansion of donor T cells (H-2kb+CD4+CD8+) (D), CD69+ T cells (E), and IFN-γ–producing T cells (F) in the spleen on day 14 after allo-BMT (n = 3-4 per group, pooled from 2 experiments). The bar shows the mean ± SEM. (G-H) The histopathological GVHD score in the GI tract (small and large intestines) (G) and liver (H) on day 14 after allo-BMT (n = 3-4 per group, pooled from 2 experiments). The bar shows the mean ± SEM. (I) In vitro MLR. Isolated splenic CD90.2+ T cells from either BALB/c or B6-WT animals were cultured with BMDCs derived from animals in the presence or absence of AT-406 (1 µM) for 96 hours and analyzed for proliferation after 3H-thymidine incorporation during the last 16 hours of incubation. A representative figure from 3 independent experiments is shown. The bar shows the mean ± SEM. (J) In vitro MLR. Isolated splenic CD90.2+ T cells from either B6-WT, B6-cIAP1−/−, or B6-XIAP−/− animals were cultured with BMDCs derived from syngeneic B6 or allogeneic BALB/c animals for 72 hours and analyzed for proliferation after 3H-thymidine incorporation during the last 16 hours of incubation. The bar shows the mean ± SEM. CPM, counts per minute.
