Adoptive transfer of CD4(+) T cells specific for subunit A of Helicobacterpylori urease reduces H-pylori stomach colonization in mice in the absenceof interleukin-4 (IL-4)/IL-13 receptor signaling

Protection in the murine model of Helicobacter pylori infection may be medi ated by CD4(+) T cells, but the mechanism remains unclear. To better unders tand how protection occurs in this model, we generated and characterized H. pylori urease-specific CD4(+) T cells from BALB/c mice immunized with Salm onella enterica serovar Typhimurium expressing H. pylori urease (subunits A and B), The CD4(+) T tells were found to be specific for subunit A (UreA). Upon antigen-specific stimulation, expression of interleukin 4 (IL-4), IL- 10, gamma interferon (INF-gamma), and tumor necrosis factor alpha was induc ed. Immunocytochemical analysis showed that the majority of cells produced IFN-gamma 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 nonrecipien t group. Stomach colonization was also reduced significantly after transfer of these cells into patently infected mice. Adoptive transfer of UreA-spec ific CD4(+) T cells into IL-4 receptor alpha chain-deficient BALB/c mice in dicated that IL-4 and IL-13 were not critical in the control of bacterial l oad. In addition, synthetic peptides were used to identify three functional T-cell epitopes present in subunit A which were recognized by the UreA-spe cific T cells. Analysis of H, pylori-specific cellular immune responses in recipient challenged and nonrecipient infected mice indicated a strong loca l restriction of the response in infected animals. The implications of thes e findings for the mechanism of protection and the development of peptide b ased vaccination are discussed.