Transplantation of IL-23^−/− marrow grafts reduces GVHD severity without loss of the GVL effect. (A-B) Lethally irradiated (900 cGy) Balb/c mice were administered 1 × 10⁵ A20 cells and then the next day transplanted with either B6 TCD BM alone (10 × 10⁶; □, n = 17; Leuk), B6 TCD BM plus B6 spleen cells (■, n = 19; GVHD), or IL-23^−/− TCD BM and spleen cells (●, n = 19). Spleen cell inoculums were adjusted so that the dose of T cells (0.6 × 10⁶) was equivalent in both groups of mice in all experiments. Survival is shown in panel A, whereas pathologic scores from surviving mice transplanted with IL-23^−/− marrow grafts (n = 12) 80 to 84 days after transplantation are shown in panel B. Data are individual GVHD target organ scores as well as the composite score (lung, liver, and colon) and are derived from cumulative results of 4 experiments. (C-D) Lethally irradiated Balb/c mice were administered 5 × 10⁵ A20 cells and then transplanted the next day with B6 TCD BM alone (□, n = 9), B6 TCD BM plus B6 spleen cells (■, n = 10), or IL-23^−/− TCD BM and spleen cells (●, n = 10). Survival is shown in panel C, whereas pathologic scores of surviving mice transplanted with IL-23^−/− marrow grafts 82 to 110 days after transplantation are shown in panel D. Data are derived from cumulative results from 2 experiments. (E) Whole body distribution of A20-luc cells over the first 60 days after transplantation using in vivo BLI is shown in animals transplanted with B6 BM only, B6 BM and spleen cells, or IL-23^−/− BM and spleen cells. Data are representative of one of 3 experiments.