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The Journal of Immunology, 2004, 172: 5024-5033.
Copyright © 2004 by The American Association of Immunologists

Helicobacter pylori-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection 1

Ali A. Akhiani2,*, Karin Schön*, Lennart E. Franzén{dagger}, Jacques Pappo{ddagger} and Nils Lycke*

* Department of Clinical Immunology, University of Göteborg, Göteborg, Sweden; {dagger} Department of Pathology, Örebro University Hospital, Örebro, Sweden; and {ddagger} Department of Immunology, AstraZeneca R&D Boston, Waltham, MA 02451

In recent years, Abs have been considered a correlate rather than an effector of resistance against Helicobacter pylori infection. However, it is still poorly understood to what extent Ab production correlates with gastric immunopathology. Here we report that Abs not only are dispensable for protection, but they are detrimental to elimination of the bacteria and appear to impair gastric inflammatory responses. We found that the initial colonization with H. pylori bacteria was normal in the B cell-deficient (µMT) mice, whereas at later times (>8 wk) most of the bacteria were cleared, concomitant with the development of severe gastritis. In contrast, wild-type (WT) mice exhibited extensive bacterial colonization and only mild gastric inflammation, even at 16 wk after inoculation. Oral immunizations with H. pylori lysate and cholera toxin adjuvant stimulated comparable levels of protection in µMT and WT mice. The level of protection in both strains correlated well with the severity of the postimmunization gastritis. Thus, T cells were responsible for the gastritis, whereas Abs, including potentially host cell cross-reactive Abs, were not involved in causing the gastritis. The T cells in µMT and WT mice produced high and comparable levels of IFN-{gamma} to recall Ag at 2 and after 8 wk, whereas IL-4 was detected after 8 wk only, indicating that Th1 activity dominated the early phase of protection, whereas later a mixed Th1 and Th2 activity was seen.




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