Donor-derived IFNγ prevents GVHD independently of effects on donor cells. Splenocytes from G-CSF–mobilized wt, IFNγ^−/−, and IFNγR^−/− B6 donors were transplanted into irradiated (1100 rad) B6D2F1 recipients (n = 18 per group). TCD splenocytes from IFNγ^−/− donors were transplanted into B6D2F1 recipients (n = 10) as non-GVHD controls. Data pooled from 2 identical experiments. (A) Survival determined by Kaplan-Meier analysis. #P < .001, recipients of IFNγ^−/− versus wt donor grafts and IFNγR^−/− versus wt. (B) GVHD clinical scores were determined as a measure of GVHD severity in surviving animals. #P < .001, recipients of IFNγ^−/− versus wt donor grafts and IFNγR^−/− versus wt. **P < .01 and *P < .05, recipients of wt grafts versus IFNγR^−/− donor grafts. Data expressed as means ± standard error (SE). (C) Semiquantitative histopathology and representative images (100 ×) of lung 14 days after BMT in recipients of wt (n = 7), IFNγ^−/− (n = 8), and IFNγ^−/− TCD grafts (n = 4). Data expressed as means ± SE of individual animals. ***P < .001, wt versus IFNγ^−/− grafts. (D) TNFα and IFNγ levels in sera of recipients of wt (n = 10), IFNγ^−/− (n = 10), and IFNγ^−/− TCD (n = 4) grafts 7 days after SCT. Data expressed as means ± SE of individual animals. ND indicates not detected. #P < .001, wt versus IFNγ^−/− grafts. (E) Donor CD4 and CD8 T-cell expansion and proportions of apoptosis within spleen of recipients of wt (n = 8) and IFNγ^−/− (n = 9) grafts 14 days after SCT. Data expressed as means ± SE of individual animals. #P < .001, **P < .01.