Transplantation of IL-23^−/− marrow grafts reduces GVHD severity without loss of the GVL effect in a chronic leukemia model. (A) Lethally irradiated FVB mice were transplanted with TCD B6 and non-TCD bcr/abl BM cells alone (□, n = 18; Leuk), TCD B6, and non-TCD bcr/abl BM cells plus B6 spleen cells adjusted to yield a T-cell dose of 3.5 × 10⁶ αβ T cells (■, n = 20; GVHD) or TCD IL-23^−/− and non-TCD bcr/abl BM cells plus IL-23^−/− spleen cells adjusted to yield the same T-cell dose (○, n = 18). Overall survival is shown. (B-C) Lethally irradiated FVB mice were transplanted with a combination of TCD B6 and non-TCD bcr/abl BM cells alone (n = 15; Leuk) or together with IL-23^−/− spleen cells (n = 15; IL-23^−/−). Mice in both groups were bled 32 to 50 days after transplantation. WBC and ANC are shown. Data are cumulative results from 3 experiments. (C) Similarly transplanted animals (n = 9/group) were killed 35 to 42 days after BMT. Spleen cellularity and the absolute number of splenic Gr-1⁺ Mac-1⁺ cells are shown. Data are cumulative results from 2 experiments and are the mean ± SEM. (D) Fold increase in bcr/abl mRNA levels over c-abl in the spleen or colon of lethally irradiated FVB mice transplanted with TCD IL-23^−/− and non-TCD bcr/abl BM cells alone (n = 9) or together with IL-23^−/− spleen cells (n = 9) analyzed 32 days after transplantation. Data are cumulative results from 2 experiments and are the mean ± SEM. (E) Lethally irradiated FVB mice were transplanted with TCD B6 and non-TCD bcr/abl BM cells alone (n = 8), TCD B6 and non-TCD bcr/abl BM cells plus B6 spleen cells adjusted to yield a T-cell dose of 3 × 10⁶ αβ T cells (n = 3), or TCD IL-23^−/− and non-TCD bcr/abl BM cells plus IL-23^−/− spleen cells adjusted to yield the same T-cell dose (n = 5). Mice were killed 28 to 29 days after transplantation, and the fold increase of bcr/abl mRNA levels over c-abl in the colon is shown. (F) Lethally irradiated FVB mice were transplanted with a combination of TCD IL-23^−/− and non-TCD bcr/abl BM cells alone (n = 4) or together with IL-23^−/− spleen cells adjusted to yield 3.5 × 10⁶ αβ T cells (n = 5). Mice were killed 80 days after transplantation, and spleen tissues were obtained from each animal to determine bcr/abl mRNA levels. Data are presented as fold increase over c-abl. *P ≤ .05. **P < .01.