Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Live Salmonella typhimurium phoPc bacteria were tested as mucosal vaccine vectors to deliver Helicobacter pylori antigens. The genes encoding the A and B subunits of H. pylori urease were introduced into S. typhimurium phoPc and expressed under the control of a constitutive tac promoter (tac-ureAB) or a two-phase T7 expression system (cT7-ureAB). Both recombinant Salmonella strains expressed the two urease subunits in vitro and were used to nasally immunize BALB/c mice. The plasmid carrying cT7-ureAB was stably inherited by bacteria growing or persisting in the spleen, lungs, mesenteric or cervical lymph nodes, and Peyer's patches of immunized mice, while the plasmid carrying tac-ureAB was rapidly lost. Spleen and Peyer's patch CD4+ lymphocytes from mice immunized with S. typhimurium phopc cT7-ureAB proliferated in vitro in response to urease, whereas cells from mice given S. typhimurium phoPc alone did not. Splenic CD4+ cells from mice immunized with phoPc cT7-ureAB secreted gamma interferon and interleukin 10, while Peyer's patch CD4+ cells did not secrete either cytokine. Specific H. pylori anti-urease immunoglobulin G1 (IgG1) and IgG2A antibodies were detected following immunization, confirming that both Th1- and Th2-type immune responses were generated by the live vaccine. Sixty percent of the mice (9 of 15) immunized with S. typhimurium phoPc cT7-ureAB were found to be resistant to infection by H. pylori, while all mice immunized with phoPc tac-ureAB (15 of 15) or phoPc (15 of 15) were infected. Our data demonstrate that H. pylori urease delivered nasally by using a vaccine strain of S. typhimurium can trigger Th1- and Th2-type responses and induce protective immunity against Helicobacter infection.
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PMID:Mice are protected from Helicobacter pylori infection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits. 945 12

Helicobacter pylori infection induces gastric inflammation but the host fails to generate protective immunity. Therefore, we evaluated the immunologic mechanisms that contribute to the failure of the T cells to promote active immunity to H. pylori in the mouse model of H. pylori infection. Spleen cells from infected C57BL/6 mice underwent significantly less proliferation and cytokine production than cells from immune mice upon in vitro stimulation with H. pylori lysate. Similar results were observed when stimulating with Ag-pulsed macrophages demonstrating that hyporesponsiveness was not due to a direct effect of H. pylori virulence factors on the T cells. Ag-specific hyporesponsiveness could be reversed by the addition of high-dose IL-2 but not by removal of CD4(+)CD25(+) T cells, indicating that hyporesponsiveness was due to anergy and not due to active suppression. Cells from infected mice lacked significant suppressor activity as shown by the failure to reduce the recall response of cells from immune mice in coculture at physiologic ratios. Direct blockade of CTLA-4 using anti-CTLA-4 Fabs or indirect blockade using CTLA-4 Ig plus anti-CD28 Ab resulted in significantly increased T cell activation in vitro. The importance of CTLA-4 in establishing anergy was confirmed in an in vivo model of H. pylori infection in which mice that received anti-CTLA-4 Fabs responded to H. pylori challenge with significantly greater inflammation and significantly reduced bacterial load. These results suggest that CTLA-4 engagement induces and maintains functional inactivation of H. pylori-specific T cells during H. pylori infection resulting in a reduced immune response.
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PMID:Induction of CTLA-4-mediated anergy contributes to persistent colonization in the murine model of gastric Helicobacter pylori infection. 1662 97