Type I-IFN signaling inhibits colon-targeted GVHD in a MHC-mismatched model of BM transplantation. Survival of lethally irradiated B6.WT or B6.IFNAR1^−/− mice undergoing transplantation at day 0 with 10⁷ BM and either (A) 5 × 10⁶ CD3⁺ T cells (*P < .05 B6.WT vs B6.IFNAR1^−/−), (B) 3 × 10⁶ CD4⁺ T cells only (**P < .01, B6.WT vs B6.IFNAR1^−/−), or (C) 2 × 10⁶ CD8⁺ T cells only from BALB/c.WT donors. In panel C, syngeneic groups received 10⁷ BM and 5 × 10⁶ CD3⁺ T cells from B6.WT donors. Combined data from 2 experiments; n = 13-14 in BM + T groups, n = 4-6 in TCD or syngeneic control groups. (D) After transplantation as in panel A, histology samples were taken at day 7 and GVHD histopathology quantified in the target organs, colon (^#P < .005, B6.WT vs B6.IFNAR1^−/−), small intestine, liver, and lung. Scores are 0 in TCD, where no bars are seen. (E) Representative images of colon histology (×250 magnification). (F) Lethally irradiated B6.WT or B6.IFNAR1^−/− recipients received BALB/c.WT BM (10⁷) + BALB/c^luc+ T cells (5 × 10⁶). Luminescence was quantified at day 7 after transplantation in mLN and GI tract as shown (**P < .01, n = 5 per group).