Figure 6.

Blockade of interleukin-7 receptor (IL-7R) and granulocyte-macrophage colony-stimulating factor (GM-CSF) mitigates graft-versus-host disease (GvHD)-associated colitis elicited by retinoic acid-related orphan receptor gamma t-deficient donor T cells. Irradiated BALB/c mice received T cell depleted bone marrow alone [no T cells (noT), n = 2] or were subsequently injected with allogeneic pan T cells of wild-type (WT) (n = 6) or Rorc^−/− mice. One group of Rorc^−/− T cell receiving mice was treated 3×/week with anti-GM-CSF antibody (αGM-CSF) throughout the experiment together with anti-IL7R (αIL-7R) until day 15 (n = 5) while another group was treated with isotype IgG antibody (n = 4) alone. Data are shown from one representative experiment. (A) Mice were evaluated 3×/week for the presence of clinical symptoms of GvHD and its severity was accordingly scored. Data were analyzed by two-way ANOVA testing followed by Bonferroni’s multiple comparisons posttest. ****p < 0.0001 was considered significant, whereas p > 0.05 indicates no significance (ns). (B) At day 29, colitis activity was assessed by colonoscopy and representative endoscopic images are shown. Data were analyzed by two-way ANOVA testing followed by Bonferroni’s multiple comparisons posttest. ***p < 0.001 was considered significant. Mice were sacrificed day 30. (C) Transcript levels of Tnf, Il1b, Ifng, and Csf2 in colonic tissue of Rorc^−/− T cell receiving mice treated with anti-GM-CSF together with anti-IL-7R or with isotype IgG antibody alone were analyzed by quantitative real-time PCR. Gene expression data were analyzed by Student’s t-test. *p < 0.05 was considered significant. All data are shown as mean ± SEM.