Figure 1.
ICOS blockade inhibits GVHD. (A) Sublethally irradiated (6.0 Gy Cs) bm12 mice were infused with the indicated number of purified CD25-depleted CD4+ T cells from B6 WT (•, 3 × 104 cells; ▪, 105) or B6 ICOS-/- mice (○, 3 × 104 cells; □, 105). Survival is shown (n = 16/group, pool of 2 experiments; P = .001 for 3 × 104 cells, P = .007 for 105 cells). (B) Sublethally irradiated (6.0 Gy Cs) bm1 mice were infused with 106 purified CD25-depleted CD8+ T cells from B6 WT (•) or B6 ICOS-/- mice (○). Survival is shown (n = 18/group, pool of 2 experiments; P = .002). (C) Lethally irradiated (8.0 Gy) BR mice received 20 × 106 B6 WT BM (*) and either 5 × 106, 15 × 106, or 25 × 106 splenocytes (indicated as 5S [circles], 15S [squares], or 25S [triangles], respectively) from B6 WT (filled symbols) or B6 ICOS-/- mice (open symbols). Survival is shown (n = 16/group, pool of 2 experiments; P ≤ .0001, B6 vs ICOS-/- at each spleen dose). (D) Lethally irradiated (8.0 Gy) BR mice received 20 × 106 B6 BM (*) and either 15 × 106 or 25 × 106 B6 splenocytes (indicated as 15S [circles] or 25S [squares], respectively). Irrelevant rIgG (filled symbols) or anti-ICOS mAb (open symbols) was administered from day -1 as indicated in “Materials and methods.” Survival is shown (n = 10-16 mice/group, 1 experiment for 25S, pool of 2 experiments for 15S and BM only; P ≤ .0006, irrel mAb vs anti-ICOS at each spleen dose). (E) Average weights are shown for mice from panel D receiving 15 × 106 splenocytes (*, BM only; •, irrelevant mAb; ○, anti-ICOS). (F) Lethally irradiated (8.0 Gy) BR mice received 20 × 106 B6 BM (*) and 25 × 106 B6 splenocytes, and rIgG (irrel mAb, •) or anti-ICOS (○) was administered starting day 5 after transplantation. Survival is shown (n = 8/group; P = .002).