Regulation of Murine Dendritic Cell Immune Responses by<i>Helicobacter felis</i>Antigen

Drakes, Maureen L.; Czinn, Steven J.; Blanchard, Thomas G.

doi:10.1128/iai.00289-06

Cited by 21 publications

(22 citation statements)

References 70 publications

(78 reference statements)

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“…4-1BBL-transfected DCs may provide dual signals; therefore, their ability to promote T cell proliferation is significantly enhanced compared with non-transfected DCs, and that is induced to secrete IFN-γ, which directly activates CD8 + T cells and further enhances the specific tumor cell killing effect. The results of our study are consistent with ones from previous studies (18,19). Therefore, the success of therapeutic vaccines will require formulations that are effective in: i) generating new immune responses, ii) boosting the existing immune responses, and iii) overcoming immune evasion mechanisms (20)(21)(22).…”

Section: Target/effector Cell Ratio (%) -----------------------------supporting

confidence: 82%

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Song

Guo

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. T cell-mediated antitumor immunity is a cellular immune response that requires two signals. The dendritic cell (DC) has been considered as the most efficient antigen-presenting cell (APC). It plays essential roles in the induction, regulation and maintenance of antitumor immunity in humans. The 4-1BB/4-1BB ligand (4-1BBL) pathway plays crucial roles in immune response, tumor immunity and autoimmune diseases through transduction of T cell co-stimulatory signals. The aim of this study was to generate the preparation protocol for a DC vaccine transfected with gastric cancer cell total ribonucleic acid (RNA) carrying the 4-1 BBL gene in vitro and to investigate its antitumor effects in murine forestomach carcinoma (MFC). The vaccine was prepared by transfecting MFC total RNAs carrying the 4-1BBL gene into the DCs that were isolated from 615 mouse bones. The T cell proliferation rate in the MFC/4-1BBL/DC group was higher than that in the DC group. The tumor cell kill rate in the MFC/4-1BBL/DC group was higher than that in the DC group. ELISA analysis showed that IL-12 and IFN-γ in the MFC/4-1BBL/DC group were more highly expressed compared to the other group. Collectively, our data demonstrate that the DC vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene has a stronger ability to kill gastric cancer cells through promoting T cell proliferation and enhancing the ability of cytotoxic T lymphocytes (CTLs) to kill gastric carcinoma cells and to secrete IL-12 and IFN-γ. Our results provide an effective therapeutic strategy for treating gastric cancer using a DC vaccine.

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Section: Target/effector Cell Ratio (%) -----------------------------supporting

confidence: 82%

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Song

Guo

et al. 2011

Experimental and Therapeutic Medicine

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“…DCs reside just beneath the surface epithelium in the normal small intestine; however, their mucosal distribution in normal gastric tissue has not been shown. We and others have demonstrated CD11c + DC recruitment in the lamina propria of mouse stomach in both acute and chronic gastritis after H pylori infection,14–16 implicating a role for these DCs in the mucosal response against H pylori . Moreover, we and others have shown that H pylori –pulsed DCs in vivo induce H pylori –specific adaptive immune responses 17.…”

Section: Introductionmentioning

confidence: 73%

Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

et al. 2010

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Background & Aims Helicobacter pylori infection increases gastric Treg response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells and thus inhibits Th17 immunity. Methods Two-photon microscopy was used to locate dendritic cells in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow–derived dendritic cells was analyzed by cytokine production and stimulation of T cell proliferation. The effect of VacA, CagA, TGF-β, and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori–specific Th17 response and H pylori density was determined using anti-CD25 neutralizing antibodies to deplete Tregs in mice. Results We showed that mucosal CD11c+ dendritic cells are located near the surface of normal gastric epithelium and their number increased after H pylori infection. Study of the direct interaction of dendritic cells with H pylori revealed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-β and IL-10. In vivo Treg skewing by adoptive transfer of H pylori–pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25+ Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori–specific Th17, but not Th1, response. Conclusions Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance towards a Treg-biased response, which suppresses the effective induction of H pylori–specific Th17 immunity.

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“…Furthermore, we and others have shown that H. pylori interactions with DCs trigger maturation and activation events that lead to the production of cytokines, which are important for the induction and regulation of immune responses (5,18,34,43,46).…”

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confidence: 99%

Helicobacter pyloriStimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4⁺T Lymphocytes

et al. 2010

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Regulation of Murine Dendritic Cell Immune Responses byHelicobacter felisAntigen

Cited by 21 publications

References 70 publications

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

Helicobacter pyloriStimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4⁺T Lymphocytes

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Regulation of Murine Dendritic Cell Immune Responses byHelicobacter felisAntigen

Cited by 21 publications

References 70 publications

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Enhanced antitumor effects of a dendritic cell vaccine transfected with gastric cancer cell total RNA carrying the 4-1BBL gene in vitro

Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

Helicobacter pyloriStimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4+T Lymphocytes

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Helicobacter pyloriStimulates Dendritic Cells To Induce Interleukin-17 Expression from CD4⁺T Lymphocytes