H Pylori
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 7, 2007; 13(21): 2923-2931
Published online Jun 7, 2007. doi: 10.3748/wjg.v13.i21.2923
CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis
Shu-Kui Wang, Hui-Fang Zhu, Bang-Shun He, Zhen-Yu Zhang, Zhi-Tan Chen, Zi-Zheng Wang, Guan-Ling Wu
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
Author contributions: All authors contributed equally to the work.
Supported by Development Foundation from Nanjing Board of Health of Jiangsu Province, China, No. ZKX05008
Correspondence to: Professor Guan-Ling Wu, Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province,China. glwu@njmu.edu.cn
Telephone: +86-25-86863187 Fax: +86-25-86862020.
Received: January 26, 2007
Revised: February 4, 2007
Accepted: February 14, 2007
Published online: June 7, 2007
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-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 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