Absence of T-bet and RORγt is sufficient to protect mice from lethal GVHD. Lethally irradiated BALB/c mice (n = 10 per group) were transplanted with 5 × 10⁶ TCD-BM alone or with 2 × 10⁶ purified T cells from WT, T-bet^−/−, RORγt^−/−, or RORγt^−/−/T-bet^−/− mice. Overall survival (A) and the percentage of original body weight over time (B) are depicted. Data are shown from 2 replicate experiments combined. (C) Lethally irradiated BALB/c mice (n = 11 per group) were transplanted with 5 × 10⁶ TCD-BM alone or with 1 × 10⁶ purified T reg-depleted T cells from WT, T-bet^−/−, RORγt^−/−, or RORγt^−/−/T-bet^−/− mice. Survival data are shown from 2 replicate experiments combined. (D) Lethally irradiated BALB/c mice (n = 6 per group) were transplanted with 5 × 10⁶ TCD-BM alone or plus total T cells at the doses indicated from WT or RORγt^−/−/T-bet^−/− mice. Survival is shown from 1 experiment with 5 recipients in each group. (E) H&E staining of colon, liver, and lung sections of recipients 20 to 25 days after HCT. (F) Pathologic score mean ± SE indicates the damage in small intestine, colon, liver, and lung using a semi-quantitative scoring system. Data are shown from 2 replicate experiments combined. Asterisk indicates statistical significance between WT and RORγt^−/−/T-bet^−/− groups: *P < .05; **P < .01; ***P < .001.