Lethally irradiated (900 cGy) Balb/c mice were transplanted with B6 bone marrow (BM) (10 × 10⁶) plus 0.4-0.5 × 10⁶ B6 spleen cells. On day 19-21 post transplantation, mice were sacrificed and spleen cells from fully donor-engrafted animals (0.45-0.5 × 10⁶) were transferred into nonirradiated B6 Rag mice. Cohorts of B6 Rag animals were then treated with either IgG1 isotype control or anti-IL-17 antibody (200 micrograms/dose) twice weekly. Mice were sacrificed 48-75 days post transfer. (A). Pathological damage in the colon, liver and lung of mice treated with isotype control (■, n=12) or anti-IL-17 antibody (□, n=12) using a semiquantitative scoring system as detailed in Methods. (B). Histology of colon, liver and lung from representative recipients treated with either isotype or anti-IL-17 antibody. In isotype control animals, colon shows inflammation in the lamina propria, and goblet cell depletion, liver reveals portal triad inflammation with mononuclear cells and endothelialitis, and lung demonstrates perivascular cuffing with mononuclear cells. In anti-IL-17 antibody-treated mice, colon also shows extensive inflammation in the lamina propria, goblet cell depletion and crypt cell destruction, liver has portal triad inflammation and lung demonstrates perivascular cuffing. (C). Total cellularity and absolute number of Gr-1⁺ Mac-1⁺ cells in the spleen are depicted. (D). Serum proinflammatory cytokine levels from B6 Rag mice treated with either isotype (n=9) or anti-IL-17 antibody (n=9) immediately prior to sacrifice of animals. (E). Absolute number of CD4⁺ and CD8⁺ T cells in the spleens of mice administered isotype (n=9) or anti-IL-17 antibody (n=9) 48-69 days post transfer. (F). Spleens and colon tissue from animals that received either control or anti-IL-17 antibody (n=3/group) were pooled and the percentage of CD4⁺ T cells secreting IL-17, IFN-γ or both cytokines in each organ is shown. Data are presented as the mean ± SEM and are the cumulative results from three to four independent experiments for all studies depicted. Statistics: **p ≤ 0.01; * p ≤ 0.05.

Lethally irradiated Balb/c mice were transplanted with BM (10 × 10⁶) and spleen cells (0.4 × 10⁶) from wild type B6 or IL-17^−/− animals to induce GVHD. Mice from each group were sacrificed 19-21 days after transplantation and pooled spleen cells (0.5 × 10⁶) were transferred into non irradiated B6 Rag mice. (A). Representative dot plot depicting the percentage of IL-17 and/or IFN-γ-secreting cells within the gated CD4⁺ T cell population obtained from the spleen, liver or colons of mice 60-65 days after transfer of spleen cells from B6→Balb/c or IL-17^−/−→Balb/c chimeras. (B,C). Individual spleens, liver and colon tissue from B6 Rag mice that received adoptive transfer of spleen cells from B6→Balb/c (■) or IL-17^−/−→Balb/c (□) chimeras (n=2-4/group) were pooled and the percentage (panel B) and absolute number (panel C) of CD4⁺ T cells secreting IFN-γ in each organ is depicted. Data are the cumulative results from three independent experiments. Each experiment had the same number of mice per group. (D). Individual spleens, livers and colon tissue from B6 Rag mice that received adoptive transfer of spleen cells from B6→Balb/c or IL-17^−/−→Balb/c chimeras (n=2-4/group) were pooled and the percentage of CD4⁺ T cells secreting IL-17 in each organ is depicted. (E). Pathological damage in the colon, liver and lung of mice 60-65 days after adoptive transfer of spleen cells from B6→Balb/c (n=9) or IL-17^−/−→Balb/c (n=9) chimeras. Data are the cumulative results from three independent experiments. Data are presented as the mean ± SEM. Statistics: * p ≤ 0.05.