Figure 1.
PD-1−/− graft and PD-1 blockade of donor T cells exacerbated GVHD, and PD-1−/− graft demonstrated inferior overall survival after HSCT. (A) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 or PD-1−/− B6 SPs with 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 = 15 per group). All animals were monitored daily for survival, and GVHD scores were estimated from days 3 to 7 and once a week from day 14. (B) Kaplan-Meier survival curve of recipient mice (syngeneic vs PD-1+/+, P < .0001; syngeneic vs PD-1+/+, P < .0001; PD-1+/+ vs PD-1−/−, P < .0001). Data from 3 same experiments were combined. (C) Mean GVHD scores of recipient mice (PD-1+/+ vs PD-1−/− on day 7, P < .05). Data are representative of 3 independent experiments. (D) Serum levels of interferon-γ (IFN-γ) on day 3 after HSCT (syngeneic vs PD-1−/−, P < .001; PD-1+/+ vs PD-1−/−, P < .0001). (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 = 5 per group). Recipient mice were injected with 600 µg of PD-1 mAb per mouse or isotype mouse IgG intraperitoneally twice weekly from day +5 to +20 after HSCT. All animals were monitored daily for survival, and GVHD scores were estimated from days 3 to 7 and once a week from day 14. (F) Representative flow cytometric histograms detecting PD-1 expression of donor CD8 T cells on day 7 after transplantation. (G) Mean GVHD scores of recipient mice treated during peritransplantation period (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .001; day 7, P < .0001; and day 28, P < .05). (H) Mean GVHD scores of recipient mice treated before transplantation (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .01; day 7, P < .001; and day 14, P < .05). Clinical scores are shown as the mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, and ****P < .0001. BMT, BM transplantation; TBI, total-body irradiation.

PD-1−/− graft and PD-1 blockade of donor T cells exacerbated GVHD, and PD-1−/− graft demonstrated inferior overall survival after HSCT. (A) Lethally irradiated BDF1 recipients received transplants of 10 × 106 PD-1+/+ B6 or PD-1−/− B6 SPs with 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 = 15 per group). All animals were monitored daily for survival, and GVHD scores were estimated from days 3 to 7 and once a week from day 14. (B) Kaplan-Meier survival curve of recipient mice (syngeneic vs PD-1+/+, P < .0001; syngeneic vs PD-1+/+, P < .0001; PD-1+/+ vs PD-1−/−, P < .0001). Data from 3 same experiments were combined. (C) Mean GVHD scores of recipient mice (PD-1+/+ vs PD-1−/− on day 7, P < .05). Data are representative of 3 independent experiments. (D) Serum levels of interferon-γ (IFN-γ) on day 3 after HSCT (syngeneic vs PD-1−/−, P < .001; PD-1+/+ vs PD-1−/−, P < .0001). (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 = 5 per group). Recipient mice were injected with 600 µg of PD-1 mAb per mouse or isotype mouse IgG intraperitoneally twice weekly from day +5 to +20 after HSCT. All animals were monitored daily for survival, and GVHD scores were estimated from days 3 to 7 and once a week from day 14. (F) Representative flow cytometric histograms detecting PD-1 expression of donor CD8 T cells on day 7 after transplantation. (G) Mean GVHD scores of recipient mice treated during peritransplantation period (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .001; day 7, P < .0001; and day 28, P < .05). (H) Mean GVHD scores of recipient mice treated before transplantation (mouse IgG vs PD-1 mAb on day 5, P < .05; day 6, P < .01; day 7, P < .001; and day 14, P < .05). Clinical scores are shown as the mean ± standard error of the mean. *P < .05, **P < .01, ***P < .001, and ****P < .0001. BMT, BM transplantation; TBI, total-body irradiation.

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