Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells

• The regulatory roles of Th1 and Th2 cells in immune protection against Helicobacter infection are not clearly understood. In this study, we report that a primary H. pylori infection can be established in the absence of IL-12 or IFN-gamma. However, IFN-gamma, but not IL-12, was involved in the development of gastritis because IFN-gamma(-/-) (GKO) mice exhibited significantly less inflammation as compared with IL-12(-/-) or wild-type (WT) mice. Both IL-12(-/-) and GKO mice failed to develop protection following oral immunization with H. pylori lysate and cholera toxin adjuvant. By contrast, Th2-deficient, IL-4(-/-), and WT mice were equally well protected. Mucosal immunization in the presence of coadministered rIL-12 in WT mice increased Ag-specific IFN-gamma-producing T cells by 5-fold and gave an additional 4-fold reduction in colonizing bacteria, confirming a key role of Th1 cells in protection. Importantly, only protected IL-4(-/-) and WT mice demonstrated substantial influx of CD4(+) T cells in the gastric mucosa. The extent of inflammation in challenged IL-12(-/-) and GKO mice was much reduced compared with that in WT mice, indicating that IFN-gamma/Th1 cells also play a major role in postimmunization gastritis. Of note, postimmunization gastritis in IL-4(-/-) mice was significantly milder than WT mice, despite a similar level of protection, indicating that immune protection is not directly linked to the degree of gastric inflammation. Only protected mice had T cells that produced high levels of IFN-gamma to recall Ag, whereas both protected and unprotected mice produced high levels of IL-13. We conclude that IL-12 and Th1 responses are crucial for H. pylori-specific protective immunity.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

Animal

Antibodies

Bacterial/biosynthesis/blood

Epitopes

T-Lymphocyte/immunology

Gastritis/genetics/immunology

Helicobacter Infections/genetics/*immunology/*prevention & control

Helicobacter pylori/*immunology

Immunization

Secondary

Immunoglobulin A/biosynthesis/blood

Immunoglobulin G/biosynthesis/blood

Interferon Type II/biosynthesis/deficiency/genetics

Interleukin-12/deficiency/genetics/*physiology

Lymphopenia/genetics/immunology

Mice

Mice

Inbred C57BL

Mice

Knockout

Support

Non-U.S. Gov't

Th1 Cells/*immunology/metabolism/pathology

Th2 Cells/immunology

*Vaccination

Publikations- och innehållstyp

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