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.
Akhiani
Ali A
AA
Department of Clinical Immunology, University of Göteborg, Göteborg, Sweden. ali.akhiani@microbio.gu.se
Pappo
Jacques
J
Kabok
Zita
Z
Schön
Karin
K
Gao
Wei
W
Franzén
Lennart E
LE
Lycke
Nils
N
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005756:Gastritis / Q000235:genetics / Q000276:immunology; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination
D000907:Antibodies, Bacterial; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018664:Interleukin-12; D007371:Interferon-gamma