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Volume 119, Issue 3, Pages (September 2000)

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Presentation on theme: "Volume 119, Issue 3, Pages (September 2000)"— Presentation transcript:

1 Volume 119, Issue 3, Pages 724-733 (September 2000)
Mice deficient in Th1- and Th2-type cytokines develop distinct forms of hapten-induced colitis  Taeko Dohi, Kohtaro Fujihashi, Hiroshi Kiyono, Charles O. Elson, Jerry R. McGhee  Gastroenterology  Volume 119, Issue 3, Pages (September 2000) DOI: /gast Copyright © 2000 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Histologic analysis of TNBS colitis. (A–D) Colon samples obtained on day 10; (E and F) samples obtained on day 2. Results for (A and E) control C57BL/6+/+ mice, (B) IL-12−/− mice, (C) IFN-γ−/− mice, and (D and F) IL-4−/− mice. (Original magnification: A and F, 20×; B–E, 10×.) Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Typical macroscopic features of TNBS colitis induced in IL-12−/− (middle, killed on day 10) and IL-4−/− (bottom, killed on day 2) mice. Normal colon taken from C57BL/6+/+ mice is seen on top. Dissected colon was opened and fixed with 5% acetic acid in ethanol. IL-12−/− mice showed diffuse inflammation with a small ulcer; IL-4−/− mice developed a large penetrating ulcer. Arrow indicates an enlarged colonic patch. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Hypertrophy of colonic patches in TNBS colitis. (A) C57BL/6+/+ mice; (B) IFN-γ−/− mice; (C) IL-12−/− mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Histologic scores of TNBS colitis. Grading was done according to criteria described previously.15 Each value is shown as the mean with an SEM. The scores for control groups given rat IgG were the same as the scores for untreated mice in each mouse group. Mouse groups indicated with asterisks had lower scores than control groups (white bars) with statistical significance. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Cytokine profiles and histologic scores in early and late phases of TNBS colitis. (A) Expression of mRNA for cytokines in freshly isolated colonic lamina propria CD4+ T cells was assessed by RT-PCR. Representative results from 3 independent experiments. Expression of mRNA for IL-10, IL-13, and TGF-β in IL-4−/− mice was not reproduced in each experiment. (B) Histologic scores for days 1 and 10. Scores were determined on days 1 (▨) and 10 (□). Each value is shown as a mean with an SEM. Asterisks indicate statistically significant difference between day 1 and day 10 in each group of mice. Score of IL-12−/− mice on day 1 (#) was significantly lower than those of C57BL/6+/+ mice or IL-4−/− mice on day 1. Grading was done as in Figure 4. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Serum levels of IFN-γ in TNBS colitis. Serum samples were obtained on days 0, 2, and 10. □, C57BL/6+/+ mice; ■, IL-12−/− mice; ○, IL-4−/− mice that died after day 2; ●, IL-4−/− mice that survived until day 10. Each point is shown as the mean of 6–17 mice with an SEM. Serum levels of IFN-γ on day 2 in C57BL/6+/+ mice were significantly higher than at day 0 or day 10. IFN-γ levels at day 2 in IL-4−/− mice that subsequently died were significantly higher than in their day 0 samples, and also higher than serum IFN-γ levels from IL-4−/− mice that survived both TNBS enemas and were killed on day 10. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions

8 Fig. 7 Characterization of TNP-specific Ab titers in serum after TNBS enema. Serum samples were obtained on day 10 after TNBS enema. Each data point shows the Ab titer of individual mice. Open circles show samples in which positive reactions were not detected at the ×28 dilution of serum. Anti-TNP IgA Ab in serum or secretory IgA in fecal extracts was low or not detected. Gastroenterology  , DOI: ( /gast ) Copyright © 2000 American Gastroenterological Association Terms and Conditions


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