Figure 5.
PTCy ameliorated GVHD caused by PD-1−/− graft and PD-1 mAb. (A) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 or PD-1−/− B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 9-15 per group). All recipient mice were intraperitoneally injected with 50 mg/kg of Cy on day 3 after HSCT. All animals were monitored daily for survival, and GVHD scores were monitored from days 3 to 7 and once per week from day 14. (B) Kaplan-Meier curve of survival after HSCT. Solid lines show outcomes of recipient mice treated with PTCy, and the dotted line shows survival without PTCy treatment (PD-1+/+ Cy+ vs PD-1−/− Cy+; ns). Data from 3 same experiments were combined. (C) Mean GVHD scores of PD-1+/+ or PD-1−/− donor mice (PD-1+/+ vs PD-1−/− on day 14, P < .05; day 21, P < .05; and day 28, P < .01). Data are representative of 3 independent experiments. (D) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 6-18 per group). Recipient mice were intraperitoneally injected with control mouse IgG or PD-1 mAb twice weekly between day −5 and +20 and were administered 50 mg/kg of Cy or vehicle on day 3 after HSCT. Mean GVHD scores of recipient mice treated with mouse IgG or peritransplantation PD-1 mAb ± PTCy (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .0001; day 7, P < .0001; day 21, P < .001; and day 28, P < .05). Data from 2 same experiments were combined. (E) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 6-10 per group). Recipient mice were intraperitoneally injected with control mouse IgG or PD-1 mAb on days −5 and −1 and were administered 50 mg/kg of Cy or vehicle on day 3 after HSCT. Mean GVHD scores of recipient mice treated with mouse IgG or pretransplantation PD-1 mAb ± PTCy (mouse IgG vs PD-1 mAb on day 6, P < .01; day 7, P < .0001; day 21, P < .01; day 28, P < .05) Data from 2 same experiments were combined. Clinical scores are expressed as the mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, ****P < .0001. *, †, ‡, and § indicate the comparison between control IgG + vehicle vs control IgG + PTCy, PD-1 mAb + vehicle vs PD-1 mAb + PTCy, control IgG + vehicle vs PD-1 mAb + vehicle, and control + PTCy vs PD-1 mAb + PTCy, respectively.

PTCy ameliorated GVHD caused by PD-1−/− graft and PD-1 mAb. (A) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 or PD-1−/− B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 9-15 per group). All recipient mice were intraperitoneally injected with 50 mg/kg of Cy on day 3 after HSCT. All animals were monitored daily for survival, and GVHD scores were monitored from days 3 to 7 and once per week from day 14. (B) Kaplan-Meier curve of survival after HSCT. Solid lines show outcomes of recipient mice treated with PTCy, and the dotted line shows survival without PTCy treatment (PD-1+/+ Cy+ vs PD-1−/− Cy+; ns). Data from 3 same experiments were combined. (C) Mean GVHD scores of PD-1+/+ or PD-1−/− donor mice (PD-1+/+ vs PD-1−/− on day 14, P < .05; day 21, P < .05; and day 28, P < .01). Data are representative of 3 independent experiments. (D) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 6-18 per group). Recipient mice were intraperitoneally injected with control mouse IgG or PD-1 mAb twice weekly between day −5 and +20 and were administered 50 mg/kg of Cy or vehicle on day 3 after HSCT. Mean GVHD scores of recipient mice treated with mouse IgG or peritransplantation PD-1 mAb ± PTCy (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .0001; day 7, P < .0001; day 21, P < .001; and day 28, P < .05). Data from 2 same experiments were combined. (E) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 SPs and 5 × 106 B6 TCD-BM cells (allogeneic group). The syngeneic group was administered the same amounts of SPs and TCD-BM cells from BDF1 mice (n = 6-10 per group). Recipient mice were intraperitoneally injected with control mouse IgG or PD-1 mAb on days −5 and −1 and were administered 50 mg/kg of Cy or vehicle on day 3 after HSCT. Mean GVHD scores of recipient mice treated with mouse IgG or pretransplantation PD-1 mAb ± PTCy (mouse IgG vs PD-1 mAb on day 6, P < .01; day 7, P < .0001; day 21, P < .01; day 28, P < .05) Data from 2 same experiments were combined. Clinical scores are expressed as the mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, ****P < .0001. *, †, ‡, and § indicate the comparison between control IgG + vehicle vs control IgG + PTCy, PD-1 mAb + vehicle vs PD-1 mAb + PTCy, control IgG + vehicle vs PD-1 mAb + vehicle, and control + PTCy vs PD-1 mAb + PTCy, respectively.

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