Transplantation with IL-27p28^−/− marrow grafts exacerbates GVHD. (A) Lethally irradiated (900 cGy) Balb/c mice were transplanted with B6 BM alone (▪, n = 5-6 per time point) or together with B6 spleen cells (adjusted to yield an αβ T-cell dose of 0.7 × 10⁶) (△, n = 5-11 per time point). Normal nontransplanted Balb/c mice served as controls (●, n = 6). Plasma IL-27p28 levels are depicted at each time point in individual animals. (B) IL-27 and IL-27R messenger RNA expression in the liver, lung, and colon of Balb/c mice transplanted with B6 BM alone (5 × 10⁶) (●, n = 10) or B6 BM and B6 spleen cells (adjusted to yield an αβ T-cell dose of 0.3 × 10⁶) (▪, n = 11) 3 weeks posttransplantation. (C-D) Lethally irradiated (900 cGy) Balb/c recipients were transplanted with B6 BM alone (●, n = 9), IL-27^−/− BM alone (○, n = 9), B6 BM and B6 spleen cells (▪, n = 15), or IL-27^−/− BM and spleen cells (□, n = 15) (adjusted to yield an αβ T-cell dose of 0.6 × 10⁶ cells). Overall survival and serial weight curves are depicted. (E) Pathological scores of liver, lung, and colon from Balb/c mice transplanted with B6 BM (black bar), IL-27^−/− BM (light gray bar), B6 BM and spleen cells (medium gray bar), or IL-27^−/− BM and spleen cells (dark gray bar) 14 days posttransplantation. Data are from 6 to 12 mice per group. (F) Representative hematoxylin and eosin–stained sections of the lung and liver of animals transplanted with B6 BM and spleen cells or IL-27^−/− BM and spleen cells as in panel E. Arrows denote areas of periportal and perivascular lymphocytic infiltration. Original magnification is ×50 for photomicrographs. (G-H) Lethally irradiated Balb/c recipients were transplanted with B6 BM alone (black bars, n = 9), IL-27^−/− BM (light gray bars, n = 9), B6 BM and B6 spleen cells (medium gray bars, n = 15), or IL-27^−/− BM and spleen cells (dark gray bars, n = 15). The absolute number (Abs No) of donor-derived CD4⁺ and CD8⁺ T cells (G) and CD4⁺ and CD8⁺ T cells that secreted IFN-γ (H) in the liver, lung, and colon 14 days posttransplantation is depicted. (I) Lethally irradiated (900 cGy) Balb.B mice were transplanted with B6 BM alone (●, n = 9), B6 BM and B6 spleen cells (▪, n = 15), or IL-27^−/− BM and spleen cells (□, n = 15) (adjusted to yield an αβ T-cell dose of 6 × 10⁶ cells). (J) Lethally irradiated (1100 cGy) B6 (▪, n = 15) or IL-27^−/− (□, n = 15) animals were transplanted with Balb/c BM and spleen cells (adjusted to a dose of 4.8 × 10⁶ αβ T cells). B6 (●, n = 9) or IL-27^−/− (○, n = 9) mice reconstituted with Balb/c BM alone served as controls. Overall survival is depicted. Results are from 2 to 3 experiments in all panels. *P < .05, **P < .01, ***P < .001.