CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.