Cure of Helicobacter pylori infection and resolution of gastritis by adoptive transfer of splenocytes in mice.
Vaccination suppresses Helicobacter pylori colonization but does not cure infection. Furthermore, postvaccination gastritis, likely induced by enhanced host response to residual colonization, may exacerbate disease. The goal of this study was to determine if adoptive transfer of C57BL/6 splenocytes to C57BL/6scid/scid (severe combined immunodeficient [SCID]) mice cures infection without exacerbating gastritis. H. pylori-infected and uninfected C57BL/6 mice and SCID recipients of normal splenocytes were killed at intervals between 5 and 51 weeks after infection. Colonization and gastritis were quantified, humoral immune responses were determined by enzyme-linked immunosorbent assay, and cellular immune responses were determined by delayed-type hypersensitivity response and by a proliferative response of cultured splenocytes to H. pylori sonicate. In infected C57BL/6 mice, gastritis developed gradually and bacterial colonization diminished but persisted throughout the experiment. In contrast, gastritis in infected recipient SCID mice developed rapidly and bacterial colonization decreased precipitously. Gastritis in those mice peaked 9 weeks after adoptive transfer, however, and began to resolve. By 45 weeks after transfer, gastritis had returned to background levels and bacteria were no longer detectable. Resolution of gastritis and elimination of infection were associated with a cellular but not humoral immune response to H. pylori antigens. These results demonstrate that although the host response fails to clear bacterial colonization in normal mice, enhanced cellular immune responses in recipient SCID mice are capable of clearing H. pylori infection and allowing resolution of gastritis. Thus, immune mechanisms of cure exist, and effective and safe vaccination protocols may be feasible.
Eaton
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Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio 43210, USA. eaton.1@osu.edu
Mefford
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D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D005756:Gastritis / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial