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


CONCLUSIONS
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.
Wang
Shu-Kui
SK
Department of Pathogen Biology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu Province, China.
Zhu
Hui-Fang
HF
He
Bang-Shun
BS
Zhang
Zhen-Yu
ZY
Chen
Zhi-Tan
ZT
Wang
Zi-Zheng
ZZ
Wu
Guan-Ling
GL
D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001706:Biopsy; D018450:Disease Progression; D016481:Helicobacter Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D009367:Neoplasm Staging; D012720:Severity of Illness Index; D013270:Stomach / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D015847:Interleukin-4; D007371:Interferon-gamma