Intraperitoneal immunization led to T cell hyporesponsiveness to Helicobacter pylori infection in mice.
During Helicobacter pylori infection, T cell response is critical in the development of active gastritis and in protective immunity against infection. We studied gastric inflammation and T cell response in H. pylori-challenged mice following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in the absence of adjuvants. H. pylori-challenged mice without immunization developed moderate to severe gastric inflammation, and splenocytes from these mice produced Th1 polarizing cytokines in response to HpAg and Con A during the acute infection. On the other hand, immunized-challenged mice (those inoculated with H. pylori following immunization) had little or no gastric inflammation despite persistent H. pylori colonization. Our immunization primed splenocytes to produce IL-2, IFN-gamma, and IL-4 in response to HpAg and Con A before infection. However, these cells became hyporesponsive to both stimulants immediately after live bacterial challenge in terms of the production of these cytokines, especially IL-2 and IFN-gamma. CTLA-4 has been documented to be a negative regulator of IL-2 production and lymphoproliferation that induces peripheral tolerance and functions 24-72 hr after the initiation of T cell activation. Compared with challenged mice, T cells from immunized-challenged mice showed higher levels of CTLA-4 expression at 72 hr after oral challenge. These data suggested that our immunization inhibited the development of H. pylori-associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA-4 following challenge.
Watanabe
Koichiro
K
Department of Microbiology, Oita Medical University, Oita, Japan.
Murakami
Kazunari
K
Maeda
Kosaku
K
Fujioka
Toshio
T
Nasu
Masaru
M
Nishizono
Akira
A
D000069594:Abatacept; D000818:Animals; D005260:Female; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000166:cytology / Q000276:immunology / Q000472:pathogenicity; D007114:Immunization; D018796:Immunoconjugates / Q000378:metabolism; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D000069594:Abatacept