Figure 7.
IFN-λ treatment protects from GVHD within the GI tract. PEG-rIL-29 or PBS was given as previously described on days −2, −1, and 0 to BMT recipients. (A) Survival by Kaplan-Meier analysis of B6 recipients transplanted with BALB/c BM + T cells (n = 10, combined from 2 experiments). (B) Survival by Kaplan-Meier analysis of B6D2F1 recipients transplanted with B6 BM + T cells (n = 10, combined from 2 experiments). (C) B6 recipients were transplanted with BALB/c BM + T cells. Serum IFN-γ and IL-6 at day 4 after BMT as in panel A (n = 15, combined from 3 experiments). (D) Representative images of colon and SI at day 7 post-BMT. (E) Semiquantitative GVHD histopathology scores at day 7 post-BMT (n = 10, combined from 2 experiments). (F) Paneth cell numbers. (G) Representative images of proliferation in colon and SI using Ki-67 at day 7 after BMT. (H-I) Quantification of Ki-67 expression at day 7 post-BMT in colon (n = 10, combined from 2 experiments) (H) and in SI (as in panel H) (I). (J) B6 recipients were transplanted with BALB/c BM ± T cells and crypt isolates obtained 7 days later. Colon organoids were quantified (n = 4, combined from 2 replicate experiments). (K-L) Representative images (K) and enumeration (L) of Lgr5+ ISCs in tissue sections at day 7 post-BMT from ileum from PBS or PEG-rIL-29 recipients of BALB/c BM + T cells after NK-cell depletion with NK1.1 on day −1 (1 mg), day +3 (0.5 mg), and day +6 (0.5 mg), (n = 9, combined from 2 experiments). (M) B6D2F1 recipients were treated with PBS or PEG-rIL-29, then transplanted with BM ± T cells from B6.WT donors, together with recipient type BCR-ABL nup98hoxA9 leukemia expressing GFP. (M) The number of GFP+ leukemia cells was determined in peripheral blood thereafter (n = 10, combined from 2 experiments). (N) Death from leukemia in recipients transplanted as in panel M. Data are presented as mean ± SEM. P values were calculated by using the 2-tailed Mann-Whitney t test. Survival was calculated by using the log-rank Mantel-Cox test. *P < .05, **P < .01, ***P < .001, ****P < .0001. DAPI, 4′,6-diamidino-2-phenylindole; TCD, T cell–depleted.

IFN-λ treatment protects from GVHD within the GI tract. PEG-rIL-29 or PBS was given as previously described on days −2, −1, and 0 to BMT recipients. (A) Survival by Kaplan-Meier analysis of B6 recipients transplanted with BALB/c BM + T cells (n = 10, combined from 2 experiments). (B) Survival by Kaplan-Meier analysis of B6D2F1 recipients transplanted with B6 BM + T cells (n = 10, combined from 2 experiments). (C) B6 recipients were transplanted with BALB/c BM + T cells. Serum IFN-γ and IL-6 at day 4 after BMT as in panel A (n = 15, combined from 3 experiments). (D) Representative images of colon and SI at day 7 post-BMT. (E) Semiquantitative GVHD histopathology scores at day 7 post-BMT (n = 10, combined from 2 experiments). (F) Paneth cell numbers. (G) Representative images of proliferation in colon and SI using Ki-67 at day 7 after BMT. (H-I) Quantification of Ki-67 expression at day 7 post-BMT in colon (n = 10, combined from 2 experiments) (H) and in SI (as in panel H) (I). (J) B6 recipients were transplanted with BALB/c BM ± T cells and crypt isolates obtained 7 days later. Colon organoids were quantified (n = 4, combined from 2 replicate experiments). (K-L) Representative images (K) and enumeration (L) of Lgr5+ ISCs in tissue sections at day 7 post-BMT from ileum from PBS or PEG-rIL-29 recipients of BALB/c BM + T cells after NK-cell depletion with NK1.1 on day −1 (1 mg), day +3 (0.5 mg), and day +6 (0.5 mg), (n = 9, combined from 2 experiments). (M) B6D2F1 recipients were treated with PBS or PEG-rIL-29, then transplanted with BM ± T cells from B6.WT donors, together with recipient type BCR-ABL nup98hoxA9 leukemia expressing GFP. (M) The number of GFP+ leukemia cells was determined in peripheral blood thereafter (n = 10, combined from 2 experiments). (N) Death from leukemia in recipients transplanted as in panel M. Data are presented as mean ± SEM. P values were calculated by using the 2-tailed Mann-Whitney t test. Survival was calculated by using the log-rank Mantel-Cox test. *P < .05, **P < .01, ***P < .001, ****P < .0001. DAPI, 4′,6-diamidino-2-phenylindole; TCD, T cell–depleted.

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