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Immunization of BALB/c mice with Helicobacter urease B induces a T helper 2 response absent in Helicobacter infection.
BACKGROUND & AIMS: Infection with Helicobacter induces a T helper type 1 response in mice and humans. Mice can be cured or protected from infection with Helicobacter by mucosal immunization with recombinant H. pylori urease B subunit (rUreB). This study characterizes the immune response of infected mice immunized with rUreB. METHODS: BALB/c mice were infected with H. felis. Two weeks later, they were orally immunized four times with rUreB and cholera toxin (CT) at weekly intervals. Controls were only infected or sham-immunized with CT. Animals were killed at various times after immunization. Splenic CD4(+) cells were obtained and cultured in vitro with rUreB to evaluate antigen-specific proliferation and induction of interferon gamma and interleukin 4 secretion. RESULTS: All rUreB-immunized mice (n = 8) were cured from infection 3 weeks after the fourth immunization. Immunization induced a proliferative response of splenic CD4(+) cells, a progressive decrease in interferon gamma secretion, and a concomitant increase in interleukin 4 secretion after each immunization. A simultaneous increase in rUreB specific serum immunoglobulin G1 levels was observed in infected/immunized mice. CONCLUSIONS: In BALB/c mice, therapeutic mucosal immunization with rUreB induces progressively a Th2 CD4(+) T cell response resulting in the elimination of the pathogen.
Animals, Antibody Formation/immunology, Cell Division/drug effects, Cholera Toxin/immunology, Cytokines/metabolism, Female, Gastric Mucosa/immunology, Gastric Mucosa/metabolism, Helicobacter/enzymology, Helicobacter Infections/immunology, Helicobacter Infections/therapy, Immunization, Isoenzymes/immunology, Mice, Mice, Inbred BALB C, Recombinant Proteins, T-Lymphocytes/pathology, T-Lymphocytes, Helper-Inducer/immunology, Th1 Cells/pathology, Th2 Cells/pathology, Urease/immunology
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