![Figure 2. PD-1/PD-L1, but not PD-1/PD-L2, blockade exacerbates acute GVHD. (A) Lethally irradiated BALB/c recipients were given 107 B6 BM cells alone or with 2 × 106 B6 T-cells and treated with isotype-matched control antibody, anti-PD-L1, anti-PD-L2, or anti-PD-L1 and anti-PD-L2 mAbs (n = 10–18/group). Kaplan–Meier survival curve of transplanted mice (isotype control vs anti-PD-L1 [P < .0001]; isotype control vs anti-PD-L2 [P = .055]; isotype control vs anti-PD-L1 and anti-PD-L2 [P = .0001]). (B) Lethally irradiated B10.BR recipients were given 107 B6 BM cells alone or with 5 × 106 B6 splenocytes and treated with isotype-matched control antibody, anti-PD-L1, or anti-PD-L2 mAb (n = 8–14/group). Kaplan–Meier survival curve of transplanted mice (isotype control vs anti-PD-L1 [P < .0001]; isotype control vs anti-PD-L2 [P = .356]). (C) Lethally irradiated wt B6 recipients or PD-L1−/−PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 5 × 106 BALB/c splenocytes (n = 14–34/group). Kaplan–Meier survival curve of transplanted mice (BM + splenocytes: wt vs PD-L1−/−PD-L2−/− recipients; P < .0001). (D) Lethally irradiated wt B6 recipients, PD-L1−/− recipients, or PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 5 × 106 BALB/c splenocytes (n = 8–17/group). Kaplan–Meier survival curve of transplanted mice (BM + splenocytes: wt vs PD-L1−/− recipients [P = .0001]; BM + splenocytes: wt vs PD-L2−/− recipients [P = .003]; BM + splenocytes: PD-L1−/− vs PD-L2−/− recipients [P = .029]). (E) Lethally irradiated wt B6 recipients or PD-L1−/−PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 1 × 106 BALB/c CD25-depleted T-cells or with 2 × 106 BALB/c CD25-depleted T-cells (n = 8/group). Kaplan–Meier survival curve of transplanted mice (BM + 1 × 106 CD25− T: wt vs PD-L1−/−PD-L2−/− recipients [P = .0006]; BM + 2 × 106 CD25− T: wt vs PD-L1−/−PD-L2−/− recipients [P = .0006]). (F) Lethally irradiated BALB/c recipients were given 107 B6 BM cells alone or with 0.75 × 106 B6 T-cells or with 0.75 × 106 B6 CD25-depleted T-cells and treated with isotype-matched control antibody or anti-PD-L1 mAbs (n = 8–10/group). Kaplan–Meier survival curve of transplanted mice (BM + T cells: isotype control vs anti-PD-L1 [P < .0001]; BM + CD25-depleted T cells: isotype control vs anti-PD-L1 [P = .074]; BM + T cells [isotype control] vs BM + CD25-depleted T cells [isotype control] [P = .0008]).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/122/17/10.1182_blood-2013-05-500801/4/3062f2.jpeg?Expires=1724246651&Signature=Kg6yaTMF--K~P6iyjdCXW3IF-h12nzG-4mQhBbddv-uZbCgct2uha6gXoQmpSyPxNnGU9Ki7nOOSCIpCb-p7~occoI5KaGjMIlASWcTVg~oYHyxV-UmRbYFevHaFEU8wP22SuyQ34BBJtMlQTqMkb4MXDPbnaR9Ee5ICQF2msXaEtMexNnPqhdKROYncQ~FA9TJM5R6kbbuWH1MSLZpzkgChshOq~sh4434IdKv5fOXn8d4pYl-0Ap~wZH~AElq1RayLNo1TANQTyLOdGwgZq6S8LOI1Qylu7IjFYRPlTjER71OpE~1JTPBA-XuMlPcuJ~ciKRDspBf5HSGd-jjoXw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
PD-1/PD-L1, but not PD-1/PD-L2, blockade exacerbates acute GVHD. (A) Lethally irradiated BALB/c recipients were given 107 B6 BM cells alone or with 2 × 106 B6 T-cells and treated with isotype-matched control antibody, anti-PD-L1, anti-PD-L2, or anti-PD-L1 and anti-PD-L2 mAbs (n = 10–18/group). Kaplan–Meier survival curve of transplanted mice (isotype control vs anti-PD-L1 [P < .0001]; isotype control vs anti-PD-L2 [P = .055]; isotype control vs anti-PD-L1 and anti-PD-L2 [P = .0001]). (B) Lethally irradiated B10.BR recipients were given 107 B6 BM cells alone or with 5 × 106 B6 splenocytes and treated with isotype-matched control antibody, anti-PD-L1, or anti-PD-L2 mAb (n = 8–14/group). Kaplan–Meier survival curve of transplanted mice (isotype control vs anti-PD-L1 [P < .0001]; isotype control vs anti-PD-L2 [P = .356]). (C) Lethally irradiated wt B6 recipients or PD-L1−/−PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 5 × 106 BALB/c splenocytes (n = 14–34/group). Kaplan–Meier survival curve of transplanted mice (BM + splenocytes: wt vs PD-L1−/−PD-L2−/− recipients; P < .0001). (D) Lethally irradiated wt B6 recipients, PD-L1−/− recipients, or PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 5 × 106 BALB/c splenocytes (n = 8–17/group). Kaplan–Meier survival curve of transplanted mice (BM + splenocytes: wt vs PD-L1−/− recipients [P = .0001]; BM + splenocytes: wt vs PD-L2−/− recipients [P = .003]; BM + splenocytes: PD-L1−/− vs PD-L2−/− recipients [P = .029]). (E) Lethally irradiated wt B6 recipients or PD-L1−/−PD-L2−/− recipients were given 107 BALB/c BM cells alone or with 1 × 106 BALB/c CD25-depleted T-cells or with 2 × 106 BALB/c CD25-depleted T-cells (n = 8/group). Kaplan–Meier survival curve of transplanted mice (BM + 1 × 106 CD25− T: wt vs PD-L1−/−PD-L2−/− recipients [P = .0006]; BM + 2 × 106 CD25− T: wt vs PD-L1−/−PD-L2−/− recipients [P = .0006]). (F) Lethally irradiated BALB/c recipients were given 107 B6 BM cells alone or with 0.75 × 106 B6 T-cells or with 0.75 × 106 B6 CD25-depleted T-cells and treated with isotype-matched control antibody or anti-PD-L1 mAbs (n = 8–10/group). Kaplan–Meier survival curve of transplanted mice (BM + T cells: isotype control vs anti-PD-L1 [P < .0001]; BM + CD25-depleted T cells: isotype control vs anti-PD-L1 [P = .074]; BM + T cells [isotype control] vs BM + CD25-depleted T cells [isotype control] [P = .0008]).
