Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine-induced protection against Helicobacter pylori in mice

• Published in: European journal of immunology 2010-10, Vol.40 (10), p.2778-2790
• Main Authors: Becher, Dorit, Deutscher, Michael E, Simpfendorfer, Kim R, Wijburg, Odilia L, Pederson, John S, Lew, Andrew M, Strugnell, Richard A, Walduck, Anna K
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Female; Flow Cytometry; Gastric Mucosa - immunology; Gastric Mucosa - microbiology; Gastritis - immunology; Gastritis - microbiology; Gastritis - prevention & control; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter Infections - prevention & control; Helicobacter pylori; Helicobacter pylori - immunology; Histocytochemistry; Immunization; Immunologic Memory - immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Rodents; Salmonella; Statistics, Nonparametric; Stomach; Th1 Cells - immunology; Treg cells; Ulcers; Vaccination - methods; Vaccine; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200940219

Helicobacter pylori is recognised as the chief cause of chronic gastritis, ulcers and gastric cancer in humans. With increased incidence of treatment failure and antibiotic resistance, development of prophylactic or therapeutic vaccination is a desirable alternative. Although the results of vaccination studies in animal models have been promising, studies in human volunteers have revealed problems such as 'post-immunisation gastritis' and comparatively poor responses to vaccine antigens. The focus of this study was to compare the gastric and systemic cellular immune responses induced by recombinant attenuated Salmonella Typhimurium-based vaccination in the C57BL/6 model of H. pylori infection. Analysis of lymphocyte populations in the gastric mucosa, blood, spleen, paragastric LN and MLN revealed that the effects of vaccination were largely confined to the parenchymal stomach rather than lymphoid organs. Vaccine-induced protection was correlated with an augmented local recall response in the gastric mucosa, with increased proportions of CD4⁺ T cells, neutrophils and reduced proportions of CD4⁺ Treg. CD4⁺ T cells isolated from the stomachs of vaccinated mice proliferated ex vivo in response to H. pylori antigen, and secreted Th1 cytokines, particularly IFN-γ. This detailed analysis of local gastric immune responses provides insight into the mechanism of vaccine-induced protection.