Affiliation:
1. Max-Planck-Institute for Infection Biology, Department of Molecular Biology, Schumannstraße 21/22, 10117 Berlin, Germany
Abstract
ABSTRACT
Protection in the murine model of
Helicobacter pylori
infection may be mediated by CD4
+
T cells, but the mechanism remains unclear. To better understand how protection occurs in this model, we generated and characterized
H. pylori
urease-specific CD4
+
T cells from BALB/c mice immunized with
Salmonella enterica
serovar Typhimurium expressing
H. pylori
urease (subunits A and B). The CD4
+
T cells were found to be specific for subunit A (UreA). Upon antigen-specific stimulation, expression of interleukin 4 (IL-4), IL-10, gamma interferon (IFN-γ), and tumor necrosis factor alpha was induced. Immunocytochemical analysis showed that the majority of cells produced IFN-γ and IL-10. Adoptive transfer of the UreA-specific CD4
+
T cells into naive syngeneic recipients led to a threefold reduction in the number of bacteria in the recipient group when compared to that in the nonrecipient group. Stomach colonization was also reduced significantly after transfer of these cells into patently infected mice. Adoptive transfer of UreA-specific CD4
+
T cells into IL-4 receptor α chain-deficient BALB/c mice indicated that IL-4 and IL-13 were not critical in the control of bacterial load. In addition, synthetic peptides were used to identify three functional T-cell epitopes present in subunit A which were recognized by the UreA-specific T cells. Analysis of
H. pylori
-specific cellular immune responses in recipient challenged and nonrecipient infected mice indicated a strong local restriction of the response in infected animals. The implications of these findings for the mechanism of protection and the development of peptide-based vaccination are discussed.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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