Donor Th1 differentiation and IFN-γ production are responsible for exacerbated cGVHD. (A-D) Sublethally irradiated BALB/c recipients were transplanted from WT or IFN-γ^−/− B10.D2 donors. Clinical skin cGVHD scores (A), pathology score of skin and lung (B), and the longest diameter of the salivary gland (C) on day 35 after BMT are shown. Four to 6 recipients were examined in each group. Data are from 1 representative of 3 independent experiments. (D) PLN cells of the recipients on day 35 were stained for intracellular Foxp3. The percentages and the absolute number of CD4⁺Foxp3⁺ Treg cells are shown. Four to 6 recipients were examined in each group. Data are from 1 representative of 2 independent experiments. (E) Sublethally irradiated BALB/c recipients were transplanted 8 × 10⁶ TCD-BM cells plus 2 × 10⁶ total spleen T cells or CD25-depleted T cells from WT or IFN-γ^−/− B10.D2 donors. The skin cGVHD scores are shown (n = 6 per group). Data are from 1 representative of ≥ 2 independent experiments. (F-H) Sublethally irradiated BALB/c recipients were transplanted from WT or IL-17^−/− B10.D2 donors. The recipients were injected with anti–IFN-γ mAbs or rat IgG (160 μg/mouse) on days 0, 5, 10, and 15 after BMT and were assessed for the clinical signs of cGVHD every 3 days. The clinical skin cGVHD scores (F), histopathology, and pathology score of the skin (G) on day 35 of BMT from WT donors. Four mice per group were used. Data are from 1 representative of ≥ 2 repeated experiments. (H) The clinical skin cGVHD scores after BMT from WT or IL-17^−/− donors are shown. Six mice per group were used. Data are from 1 representative of 2 independent experiments. The means (± SEs) of each group are shown; *P < .05.