Figure 1
Figure 1. Combined rapamycin/Treg treatment had a synergistic protective effect against aGvHD. BALB/c mice were injected with 5 × 106 TCD-BM cells alone (●) or together with 1.6 × 106 CD4+/CD8+ (1:4) T cells and Tregs when indicated (both H-2kq) after lethal irradiation at 800 cGy. (A) Percentage survival of animals receiving conventional T cells (Tconv) + PBS (△, n = 10), T cells and rapamycin (RAPA) 0.5 mg/kg (*, n = 10), Treg:Tconv (1:8) + PBS (□, n = 10), or Treg:Tconv (1:8) + RAPA (○, n = 10). The combination of Tregs with RAPA compared with Tregs with PBS improves survival (○ versus □, P = .003). Survival data from 2 independent experiments are combined. (B) Weight change of animals in the different groups. Animals receiving Treg:Tconv (1:8) in combination with RAPA compared with PBS experience less-pronounced weight loss and recover to their baseline weight. (C) Survival of animals receiving conventional T cells (Tconv) only (△, n = 10), Tconv and RAPA 0.5 mg/kg (*, n = 10), Treg:Tconv (1:4) + PBS (□, n = 10), or Treg:Tconv (1:4) + RAPA (○, n = 10). The combination of Tregs with RAPA compared with Tregs with PBS improves survival (○ versus □, P = .007). Survival data from 2 independent experiments are combined. (D) Animals receiving Treg:Tconv (1:4) in combination with RAPA compared with PBS experience less weight loss after transplantation. (E) Twelve days after transplantation, 5 mice from each group were killed and samples of liver, small bowel, and large bowel were analyzed for evidence of pathologic damage. Hematoxylin and eosin stains of colon tissue obtained from these mice are shown. Tissue section from the colon of mice receiving TCD-BM (i), with Tconv (ii), Tconv and RAPA (0.5 mg/kg) (iii), Treg:Tconv (1:8) + PBS (iv), Treg:Tconv (1:8) + RAPA (v). Colon tissue from TCD-BM (i) and Treg:Tconv (1:8) + RAPA (v) displays intact crypts with goblet cells. The other groups have crypt abscesses (black arrows), sloughing of the colonic mucosa (blue arrows), destruction of the crypt, and loss of goblet cells. (vi) Cumulative GVHD histopathology scoring for large bowel, small bowel, and livers of animals from the indicated groups, *P < .05.

Combined rapamycin/Treg treatment hada synergistic protective effect against aGvHD. BALB/c mice were injected with 5 × 106 TCD-BM cells alone (●) or together with 1.6 × 106 CD4+/CD8+ (1:4) T cells and Tregs when indicated (both H-2kq) after lethal irradiation at 800 cGy. (A) Percentage survival of animals receiving conventional T cells (Tconv) + PBS (△, n = 10), T cells and rapamycin (RAPA) 0.5 mg/kg (*, n = 10), Treg:Tconv (1:8) + PBS (□, n = 10), or Treg:Tconv (1:8) + RAPA (○, n = 10). The combination of Tregs with RAPA compared with Tregs with PBS improves survival (○ versus □, P = .003). Survival data from 2 independent experiments are combined. (B) Weight change of animals in the different groups. Animals receiving Treg:Tconv (1:8) in combination with RAPA compared with PBS experience less-pronounced weight loss and recover to their baseline weight. (C) Survival of animals receiving conventional T cells (Tconv) only (△, n = 10), Tconv and RAPA 0.5 mg/kg (*, n = 10), Treg:Tconv (1:4) + PBS (□, n = 10), or Treg:Tconv (1:4) + RAPA (○, n = 10). The combination of Tregs with RAPA compared with Tregs with PBS improves survival (○ versus □, P = .007). Survival data from 2 independent experiments are combined. (D) Animals receiving Treg:Tconv (1:4) in combination with RAPA compared with PBS experience less weight loss after transplantation. (E) Twelve days after transplantation, 5 mice from each group were killed and samples of liver, small bowel, and large bowel were analyzed for evidence of pathologic damage. Hematoxylin and eosin stains of colon tissue obtained from these mice are shown. Tissue section from the colon of mice receiving TCD-BM (i), with Tconv (ii), Tconv and RAPA (0.5 mg/kg) (iii), Treg:Tconv (1:8) + PBS (iv), Treg:Tconv (1:8) + RAPA (v). Colon tissue from TCD-BM (i) and Treg:Tconv (1:8) + RAPA (v) displays intact crypts with goblet cells. The other groups have crypt abscesses (black arrows), sloughing of the colonic mucosa (blue arrows), destruction of the crypt, and loss of goblet cells. (vi) Cumulative GVHD histopathology scoring for large bowel, small bowel, and livers of animals from the indicated groups, *P < .05.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal