1. Volume 136, Issue 1, Pages 278-287 (January 2009)
CpG Motifs of Bacterial DNA Exert Protective Effects in Mouse Models of IBD by Antigen-Independent Tolerance Induction 
Andre Bleich, Lydia M. Janus, Anna Smoczek, Astrid M. Westendorf, Ulrike Strauch, Michael Mähler, Hans-J. Hedrich, Stefan Fichtner- Feigl, Jürgen Schölmerich, Werner Falk, Claudia Hofmann, Florian Obermeier 
Gastroenterology 
Volume 136, Issue 1, Pages (January 2009)
DOI: /j.gastro
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2. Figure 1
Effects of CpG-ODN treatment of germ-free donor mice in the SCID-transfer model of colitis. Germ-free sham-treated (GF), germ-free CpG-ODN (GF-CpG), germ-free control ODN (GF-GpG), or untreated SPF (SPF) BALB/cZtm mice were used for the isolation of splenic CD4+CD62L+ cells, which were then transferred to CB17-Prkdcscid recipients. After 8 weeks, severity of colitis was examined using a histologic score, and cytokine secretion from anti-CD3–stimulated pooled mesenteric lymph node cells was determined. The result is representative of 2 independent experiments. Bars represent mean ± SD.
Gastroenterology  , DOI: ( /j.gastro )
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3. Figure 2
Cytokine secretion pattern and FOXP3 staining of CD4+CD62L+ spleen cells isolated from germ-free mice that were treated with CpG-ODN (GF-CpG), control ODN (GF-GpG) or sham treated (GF). (A) CD4+CD62L+ cells were stimulated with anti-CD3/anti-CD28 in quadruplicates for 24 hours. Proinflammatory cytokines were detected in the supernatants by ELISA. (B) FACS staining of CD4+CD62L+ cells (n = 3–4 per group).
Gastroenterology  , DOI: ( /j.gastro )
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4. Figure 3
Colitis development in CB17-Prkdcscid recipients and cytokine secretion of mesenteric lymph node cells after cotransfer of CD4+CD62+ lymphocytes from CpG-ODN and sham-treated germ-free donors. As determined by histology, recipients were equally protected after cotransfer or transfer of cells from CpG-ODN–treated donors compared with controls that received cells from sham-treated donors. Furthermore, significantly elevated IL-10 and decreased IFN-γ secretion was observed after cotransfer compared with controls.
Gastroenterology  , DOI: ( /j.gastro )
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5. Figure 4
CpG-ODN treatment of IL-10−/− mice. (A) Germ-free B6-IL-10−/− mice were ODN treated and transferred into a conventional SPF environment and necropsied 16 weeks after transfer. (B) Conventional SPF B6-IL-10−/− mice were ODN or sham treated before the onset of colitis. Colitis development was measured by the histologic score as described in the Materials and Methods section. (C) Detection of regulatory T-cell markers by FACS analysis of CD4+CD62L+ lymphocytes isolated from germ-free B6-IL-10−/− mice. A significantly higher proportion of FOXP3+, PD-1+, and CD25+ cells was detected in CD4+CD62L+ lymphocytes of CpG-ODN–treated B6-IL-10−/− mice (GF-CpG) compared with cells of control mice (GF-GpG, GF-Null). (D) Transfer of CD4+CD62L+ lymphocytes from PBS or sham-treated germ-free BALB/c-IL-10−/− mice to CB17-Prkdcscid recipients. No significant protection was observed after CpG-ODN treatment of donors.
Gastroenterology  , DOI: ( /j.gastro )
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6. Figure 5
Effect of anti-IFN-α/β or anti-TGF-β treatment during CpG-ODN administration to germ-free BALB/c-donors on colitis development in recipients (A) and cytokine secretion of anti-CD3–/anti-CD28–stimulated mesenteric lymph node cells (B). Neutralization of either cytokine led to reversal of the CpG-ODN effect on colitis development (histology, TNF levels) and IL-10 secretion in recipients, but only anti-IFN-α/β affected IFN-γ and IL-17 secretion. The same letters above 2 bars indicate that no statistically significant differences were detected between the respective groups; otherwise, P values are shown. Control rat IgG application during CpG-ODN treatment served as a control (CpG-control).
Gastroenterology  , DOI: ( /j.gastro )
Copyright © 2009 AGA Institute Terms and Conditions