Figure 1.
TIM-1 blockade protects transplant recipients from lethal GVHD. (A) Overall survival of allogeneic transplanted BALB/c recipient mice (n = 5 per group) after injection of only TCD BM and FVB/N Tcon cells (▼) or TCD BM, FVB/N Tcon cells, and anti–TIM-1 mAb (3D10; 400 μg given IP) (●). Pooled data are from 2 independent experiments (n = 10 per group). (B) Overall survival of allogeneic transplanted BALB/c recipient mice after transplantation with TCD BM and treatment with B6 Tcon cells alone (▼), Tcon cells and anti–TIM-1 mAb (3D10; 400 μg given IP) (●), or Tcon cells and anti-TIM-4 mAb (21H12; 400 μg given IP) (▪). Pooled data of 2 independent experiments are shown (n = 10 mice per group). Control mice received TCD BM only (☐). The log-rank test was used for statistical evaluation of mouse survival (Kaplan-Meier survival curves), with comparison of Tcon cells to Tcon cells and anti–TIM-1 mAb shown. (C) Representative photomicrographs of hematoxylin and eosin–stained sections of gut tissues (magnification ×200). BALB/c mice that received allogeneic Tcon cells and isotype mAb exhibit intestinal mucosa with increased crypt apoptosis and reactive epithelial changes. Focal crypt loss is seen (middle panel). BALB/c mice that that received Tcon cells + anti–TIM-1 mAb (3D10) exhibit intestinal mucosa with well-preserved villi and crypts. No histological evidence of GVHD is seen (right panel). (D) GVHD histology score as assessed by a histopathologist in a blinded fashion (n = 10 per group). (E) Overall survival of allogeneic transplanted WT BALB/c mice (▼) or TIM-1−/− knockout BALB/c recipient mice (▲) after transplantation with B6 TCD-BM and Tcon cells . Pooled data from 2 independent experiments are shown (n = 10 mice per group). Control mice that received TCD-BM only are indicated (☐). The log-rank test was used for statistical evaluation of mouse survival (Kaplan-Meier survival curves). (F) Overall survival of NSG mice transplanted with only Hu-PBMCs (◯) or PBMCs and anti-human TIM-1 mAb (1D12) (●). Statistically significant improved survival and a GVHD score are reported as pooled data from 2 independent experiments (n = 8 mice per group; 2-tailed Student t test). *P ≤ .05, **P ≤ .01, ***P ≤ .001. Error bars indicate standard error of the mean (SEM). Black arrows indicate anti–TIM-1 (3D10) mAb administration in relation to HCT (days −1, 3, 7, and 11). ns, not significant.

TIM-1 blockade protects transplant recipients from lethal GVHD. (A) Overall survival of allogeneic transplanted BALB/c recipient mice (n = 5 per group) after injection of only TCD BM and FVB/N Tcon cells (▼) or TCD BM, FVB/N Tcon cells, and anti–TIM-1 mAb (3D10; 400 μg given IP) (●). Pooled data are from 2 independent experiments (n = 10 per group). (B) Overall survival of allogeneic transplanted BALB/c recipient mice after transplantation with TCD BM and treatment with B6 Tcon cells alone (▼), Tcon cells and anti–TIM-1 mAb (3D10; 400 μg given IP) (●), or Tcon cells and anti-TIM-4 mAb (21H12; 400 μg given IP) (▪). Pooled data of 2 independent experiments are shown (n = 10 mice per group). Control mice received TCD BM only (☐). The log-rank test was used for statistical evaluation of mouse survival (Kaplan-Meier survival curves), with comparison of Tcon cells to Tcon cells and anti–TIM-1 mAb shown. (C) Representative photomicrographs of hematoxylin and eosin–stained sections of gut tissues (magnification ×200). BALB/c mice that received allogeneic Tcon cells and isotype mAb exhibit intestinal mucosa with increased crypt apoptosis and reactive epithelial changes. Focal crypt loss is seen (middle panel). BALB/c mice that that received Tcon cells + anti–TIM-1 mAb (3D10) exhibit intestinal mucosa with well-preserved villi and crypts. No histological evidence of GVHD is seen (right panel). (D) GVHD histology score as assessed by a histopathologist in a blinded fashion (n = 10 per group). (E) Overall survival of allogeneic transplanted WT BALB/c mice (▼) or TIM-1−/− knockout BALB/c recipient mice (▲) after transplantation with B6 TCD-BM and Tcon cells . Pooled data from 2 independent experiments are shown (n = 10 mice per group). Control mice that received TCD-BM only are indicated (☐). The log-rank test was used for statistical evaluation of mouse survival (Kaplan-Meier survival curves). (F) Overall survival of NSG mice transplanted with only Hu-PBMCs (◯) or PBMCs and anti-human TIM-1 mAb (1D12) (●). Statistically significant improved survival and a GVHD score are reported as pooled data from 2 independent experiments (n = 8 mice per group; 2-tailed Student t test). *P ≤ .05, **P ≤ .01, ***P ≤ .001. Error bars indicate standard error of the mean (SEM). Black arrows indicate anti–TIM-1 (3D10) mAb administration in relation to HCT (days −1, 3, 7, and 11). ns, not significant.

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