Fig. 5. Gut-aGVHD induced by IFN-γ^−/− donor CD8⁺ T cells is Tc22-dependent.

a, b Gut-aGVHD was induced in BALB/c recipients with grafts from IFN-γ^−/− or IFN-γ^−/−/IL-17^−/− C57BL/6 donors as described in Fig. 4a. a Plots of %mice without diarrhea, %Original bodyweight and %survival. n = 8. b Means ± SEM of percentages of IL-17A⁻IL-22⁺ CD8⁺ T cells in MLN at 7 days after HCT are shown. n = 4. c–e WT BALB/c recipients with gut-aGVHD induced with grafts from IFNγ^−/− C57BL/6 donors were treated with anti-IL-22 mAb or control IgG. c Plots of %mice without diarrhea and %survival; n = 10. d Mean ± SEM of %IL-17A⁺IL-22⁻, IL-17A⁺IL-22⁺, or IL-17A⁻IL-22⁺ CD8⁺ T-cell subsets in MLN at day 7. n = 8. e % and yield of neutrophils in the colon at day 10. n = 6 (IgG), 7 (anti-IL-22). f, g WT BALB/c with grafts from WT or IFNγ^−/− C57BL/6 donors were measured for ileal expression of Reg3γ and serum Reg3γ at days 7 and 14. Mean ± SEM, n = 4 (f, d7), 6 (f, d14, WT), 9 (f, d14, IFNγ^−/− & g, d14, WT), 8 (g, d7, WT), 11 (g, d7, IFNγ^−/−), 7 (g, d14, IFNγ^−/−). h Mean ± SEM of Ileal Reg3γ mRNA and serum Reg3γ in anti-IL-22 and IgG groups at day 7. n = 5 (mRNA), 10 (Serum, IgG), 7 (Serum, anti-IL-22). i–k Lethally irradiated WT or Reg3γ^−/− C57BL/6 recipients were engrafted with WT-TCD-BM (2.5 × 10⁶) and CD8⁺ T cells (2.5 × 10⁶) from IFN-γ^−/− BALB/c donors, and recipients for monitored for Gut GVHD and survival. i Day 7, Mean ± SEM of %IL-17A⁺IL-22⁻, IL-17A⁺IL-22⁺ or IL-17A⁻IL⁻22⁺ CD8⁺ T cells in MLN, n = 9. j Day 7, means ± SEM of ileal Reg3γ mRNA expression are shown, n = 5. k Plots of %survival, n = 8 (WT), 6 (Reg3γ^−/−). All results are combined from two replicates. Each dot represents one mouse. Nonlinear regression (curve fit) was performed with two-tailed p value for bodyweight and diarrhea comparisons. Log-rank test was used with two-tailed p value for survival comparison. Unpaired two-tailed Student’ t test was used to compare means between two groups. a ****p < 0.0001; c ***p = 0.003, ****p < 0.0001; e **p = 0.0022, ***p = 0.0010; f ****p < 0.0001, *p = 0.0127; g *p = 0.0103, ** p = 0.0063; h **p = 0.0047, ****p < 0.0001; j **p = 0.0031; k **p = 0.0021. T-cell-depleted bone marrow (TCD-BM).