Attenuation of immune-mediated BM destruction with IFN-γR1 gene disruption. B6 mice and IFN-γR1^−/− mice were treated with 6.5 Gy TBI (B6 control; n = 7; IFN-γR1^−/− control; n = 10) or TBI plus infusion of 5 × 10⁶ FVB LN cells (B6 BM failure; n = 10; IFN-γR1^−/− BM failure; n = 8). Mice were bled and euthanized at day 12 to measure complete blood count (CBC) and cellular change. (A) B6 mice treated with FVB LN cells had severe declines in white blood cells (WBCs; 88%), RBCs (40%), platelets (40%), and total BM cells (57%) relative to TBI-only controls, whereas IFN-γR1^−/− mice infused with FVB LN cells had only a 40% decline in WBCs relative to TBI-only controls without decreases in RBCs, platelets, or total BM cells, leading to significant differences (P < .01) between B6 and IFN-γR1^−/− mice in response to the same number of infusions with FVB LN cells. (B) IFN-γR1^−/− mice infused with FVB LN cells had lower proportions of CD4 and CD8 T cells (P < .05) in BM relative to B6 mice infused with FVB LN cells. (C) B6 mice infused with FVB LN cells (n = 6) had a significantly higher (P < .05) proportion of Fas⁺ cells in CD4^–CD8^– residual BM cells relative to their TBI-only controls (n = 4). IFN-γR1^−/− mice (n = 5) infused with FVB LN cells showed no Fas upregulation on residual BM cells relative to their TBI-only controls (n = 6). (D) B6 mice, but not IFN-γR1^−/− mice, infused with FVB LN cells had a significantly reduced proportion and total number of KLCD150⁺ hematopoietic stem and progenitor cells relative to their respective TBI-only controls, leading to significant treatment and strain interactions (P < .01).