Antibody blockade of IL-23 significantly enhances immune reconstitution and results in selective GVHD protection in the colon. (A-D) Lethally irradiated Balb/c mice were transplanted with B6 BM alone (n = 5) or B6 BM and spleen cells adjusted to yield 0.225 to 0.4 × 10⁶ T cells. Cohorts of animals transplanted with adjunctive spleen cells were then treated with either isotype control (n = 11) or p19 antibody (n = 15). Spleen cellularity (A), total number of splenic B cells (B), thymus size (C), absolute number of double-positive (CD4⁺CD8⁺) thymocytes (D), and pathologic damage in GVHD target tissues (colon, liver, and lung; E) in mice 3 to 4 weeks after transplantation are shown. Data are derived from cumulative results from 3 experiments and are presented as the mean ± SEM. (F) Histology of colon, liver, and lung from representative Balb/c recipients 3 to 4 weeks after transplantation with B6 BM and spleen cells and then treated with either isotype control or p19 antibody. Colon in isotype-treated mouse shows inflammation in the lamina propria, extensive crypt cell destruction, and goblet cell depletion, whereas colon in p-19-treated animal has normal-appearing mucosa with no inflammatory infiltration and preserved goblet cell content. Livers in both mice show infiltration in the portal triads with mononuclear and granulocytic cells. Lungs demonstrate peribronchial and/or perivascular cuffing attributable to mononuclear and granulocytic cells along with associated interstitial inflammation. Images were obtained with an Olympus DP70 digital camera and an Olympus BX45 microscope with a 20×/0.5 NA lens. *P ≤ .05. **P < .01.