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CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis
引用本文:Wang SK,Zhu HF,He BS,Zhang ZY,Chen ZT,Wang ZZ,Wu GL. CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis[J]. World journal of gastroenterology : WJG, 2007, 13(21): 2923-2931. DOI: 10.3748/wjg.v13.i21.2923
作者姓名:Wang SK  Zhu HF  He BS  Zhang ZY  Chen ZT  Wang ZZ  Wu GL
作者单位:Shu-Kui Wang,Guan-Ling Wu,Department of Pathogen Biology,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China Shu-Kui Wang,Hui-Fang Zhu,Bang-Shun He,Zhen-Yu Zhang,Zhi-Tan Chen,Zi-Zheng Wang,Affiliated Nanjing First Hospital,Nanjing Medical University,Nanjing 210006,Jiangsu Province,China Hui-Fang Zhu,Bang-Shun He,College of Life Sciences,Nanjing Normal University,Nanjing 210097,Jiangsu Province,China
摘    要:
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.

关 键 词:胃癌  免疫应答  T细胞  幽门螺杆菌病
收稿时间:2007-01-26

CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis
Wang Shu-Kui,Zhu Hui-Fang,He Bang-Shun,Zhang Zhen-Yu,Chen Zhi-Tan,Wang Zi-Zheng,Wu Guan-Ling. CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis[J]. World journal of gastroenterology : WJG, 2007, 13(21): 2923-2931. DOI: 10.3748/wjg.v13.i21.2923
Authors:Wang Shu-Kui  Zhu Hui-Fang  He Bang-Shun  Zhang Zhen-Yu  Chen Zhi-Tan  Wang Zi-Zheng  Wu Guan-Ling
Affiliation:1. Department of Pathogen Biology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China;Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
2. Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China;College of Life Sciences,Nanjing Normal University, Nanjing 210097, Jiangsu Province,China
3. Affiliated Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
4. Department of Pathogen Biology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Abstract:
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-gamma and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test, urea [(14)C] 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 pylori infection, 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.
Keywords:H pylori  CagA  Gastric carcinogenesis  T helper cells  Regulatory T cells  Immune response
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