Figure 2.
TNF-α–deficient mice are resistant to immune-mediated BM failure. (A) WT C57BL/6 (B6) mice or B6 mice carrying germline deletion of TNF-α (TNF-α−/−) were irradiated with 6.5 Gy TBI without (TBI) or with infusion of 5 × 106 LN cells (TBI+LN) from FVB donors to induce BM failure. Animals were evaluated at day 10. (B) Histology of sternums from B6 or TNF-α−/− mice that received TBI or TBI+LN infusion (original magnification ×200; hematoxylin and eosin stain). (C) B6 mice that received TBI+LN infusion (n = 10) showed declines in WBCs, platelets, and total BM cells relative to TBI controls (n = 8), whereas TNF-α−/− animals that received TBI+LN infusion (n = 5) showed no decline in blood or BM cells relative to TBI controls (n = 4). (D) TBI+LN infusion caused significant declines in BM total CFU, CFU-G, CFU-M, and CFU-GM in B6 mice, whereas no such decline was detected in TBI+LN-infused TNF-α−/− mice. (E) Fas expression on total BM cells was increased in B6, but not in TNF-α−/−, recipient mice following FVB LN-cell injection. (F) Blood plasma concentrations of IFN-γ and TNF-α increased drastically in B6, but not in TNF-α−/−, recipient mice following FVB LN-cell infusion, relative to their respective TBI controls. *P < .05; **P < .01; ***P < .001; ****P < .0001.