title: Helicobacter pylori antigens as potential modulators of lymphocytes' cytotoxic activity.
abstract: Helicobacter pylori (H.p) colonizes human gastric mucosa and causes gastric and duodenal ulcer disease or gastric cancer. Various H.p compounds may modulate the host immune response in regards to tolerance of the infection or disease development. The aim of this study was to determine whether H.p lipopolysaccharide (LPS) and glycine acid extract antigens (GE) or E. coli LPS influence the cytotoxic activity of peripheral blood lymphocytes from H.p infected - H.p (+) or uninfected - H.p (-) individuals, in the presence or absence of exogenous interleukin (IL)12. Individual H.p status was defined by the urea breath test. Lymphocytes, stimulated or not with H.p, and control antigens, with or without IL-12, were used as effector cells and epithelial HeLa cells as targets. The cytotoxicity of lymphocytes was expressed as the percentage of dead target cells unable to reduce tetrazolium salt. The supernatants from HeLa/lymphocyte cultures were used for detection of the cellular cytotoxicity markers granzyme B and caspase 8. The natural cytotoxic activity of lymphocytes from H.p (+) was less than that of H.p (-) donors. This may have been due to fewer natural killer cells of CD3(-) CD56(+) Nkp46(+)  phenotype in H.p (+) in comparison to H.p (-) subjects. H.p GE and standard E. coli LPS enhanced the cytotoxicity of lymphocytes towards target cells whereas H.p LPS downregulated this activity. The decrease in lymphocyte cytotoxicity in response to H.p LPS correlated with a lack of IL-2 and IL-12 production, inhibition of interferon-γ production, and low IL-10 secretion by mononuclear leukocytes. IL-12 significantly enhanced the natural as well as H.p LPS and H.p GE driven cytotoxic capacity of lymphocytes. In conclusion, H.p LPS may negatively modulate natural cytotoxic activity and cytokine secretion by immunocompetent cells and thus be involved in the maintenance of infection and development of gastric pathologies.
authors: Department of Immunology and Infectious Biology, University of Łódź, Banacha 12/16, 90-237, Łódź, Poland.
authors: Karolina
authors: K
authors: Rudnicka
authors: Marcin
authors: M
authors: Włodarczyk
authors: Anthony P
authors: AP
authors: Moran
authors: Tomasz
authors: T
authors: Rechciński
authors: Eliza
authors: E
authors: Miszczyk
authors: Agnieszka
authors: A
authors: Matusiak
authors: Ewelina
authors: E
authors: Szczęsna
authors: Maria
authors: M
authors: Walencka
authors: Wiesława
authors: W
authors: Rudnicka
authors: Magdalena
authors: M
authors: Chmiela
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001944:Breath Tests / Q000379:methods; D053181:Caspase 8 / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology; D005998:Glycine / Q000494:pharmacology; D053804:Granzymes / Q000378:metabolism; D006367:HeLa Cells; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D008875:Middle Aged; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D003470:Culture Media; C508609:IL10 protein, human; D007376:Interleukin-2; D008070:Lipopolysaccharides; D013778:Tetrazolium Salts; C442865:lipopolysaccharide, Helicobacter pylori; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes; D053181:Caspase 8; D005998:Glycine