Combination of RAPA and IL-2 protects animals from acute GVHD by reducing alloreactive T-cell expansion in vivo. BALB/c mice were treated with irradiation alone (800 cGy; ●) or injected with 5 × 106 TCD-BM cells alone (■) or together with 1 × 106luc+ Tcons after lethal irradiation. Each group of mice received PBS (▴), RAPA (▾), IL-2 alone (♦) or a combination of RAPA plus IL-2 (○). Treatment of RAPA was continued until 14 days after BMT and IL-2 was administrated intraperitoneally before BMT and then twice a day thereafter for 3 days. Mice receiving the combination of RAPA + IL-2 had lower acute GVHD score than those receiving RAPA or IL-2 alone (A). (B) Expansion of luciferase-expressing T cells as quantified by total emitted photons per mouse at serial time points after BMT. Signal intensity is significantly lower in mice receiving a combination of RAPA + IL-2 compared with PBS (P < .05) or IL-2 alone (P < .01). (C) Single time points showing the expansion of luc+ donor T cells in BALB/c mice in the different groups. T-cell expansion was reduced in mice receiving the combination of RAPA + IL-2 compared with RAPA alone at day 21 after BMT or IL-2 alone at day 9 and day 21 after BMT. (D) Survival of mice in the different groups (n = 15 per group). Lethal acute GVHD induced by C57BL/6 Tcons in BALB/c recipients was reduced in animals treated with the combination of RAPA + IL-2 (○ versus ▴, P < .0001; ○ versus ♦, P = .007). Error bars represent SEM.
