Helicobacter pylori antigen-specific T-cell responses at gastric level in chronic gastritis, peptic ulcer, gastric cancer and low-grade mucosa-associated lymphoid tissue (MALT) lymphoma

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

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Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses

Gut ◽

10.1136/gut.2007.137539 ◽

2008 ◽

Vol 57 (10) ◽

pp. 1375-1385 ◽

Cited By ~ 128

Author(s):

K Robinson ◽

R Kenefeck ◽

E L Pidgeon ◽

S Shakib ◽

S Patel ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

T Cell ◽

Peptic Ulcer Disease ◽

Regulatory T Cell ◽

T Cell Responses ◽

Ulcer Disease ◽

Cell Responses

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Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Synergizes with Local Lymph Nodes during Antiviral CD4+ T Cell Responses

Lymphatic Research and Biology ◽

10.1089/lrb.2013.0015 ◽

2013 ◽

Vol 11 (4) ◽

pp. 196-202 ◽

Cited By ~ 20

Author(s):

Laura E. Richert ◽

Ann L. Harmsen ◽

Agnieszka Rynda-Apple ◽

James A. Wiley ◽

Amy E. Servid ◽

...

Keyword(s):

T Cell ◽

Lymph Nodes ◽

Lymphoid Tissue ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses

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Effective CD4+ T-cell restoration in gut-associated lymphoid tissue of HIV-infected patients is associated with enhanced Th17 cells and polyfunctional HIV-specific T-cell responses

Mucosal Immunology ◽

10.1038/mi.2008.35 ◽

2008 ◽

Vol 1 (6) ◽

pp. 475-488 ◽

Cited By ~ 127

Author(s):

M Macal ◽

S Sankaran ◽

T-W Chun ◽

E Reay ◽

J Flamm ◽

...

Keyword(s):

T Cell ◽

Lymphoid Tissue ◽

Th17 Cells ◽

T Cell Responses ◽

Cd4 T Cell ◽

Cell Responses

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Helicobacter pyloriAnti-CagA Antibodies: Prevalence in Symptomatic and Asymptomatic Subjects in Turkey

Canadian Journal of Gastroenterology ◽

10.1155/2002/589087 ◽

2002 ◽

Vol 16 (8) ◽

pp. 527-532 ◽

Cited By ~ 13

Author(s):

M Fatih Abasiyanik ◽

Ersan Sander ◽

Barik A Salih

Keyword(s):

Gastric Cancer ◽

Duodenal Ulcer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Chronic Gastritis ◽

Molecular Weights ◽

Cancer Antigens ◽

Gastroduodenal Disease ◽

H Pylori ◽

Asymptomatic Subjects

BACKGROUND: Several reports have shown the prevalence of anti-CagA antibodies to be associated with the development of peptic ulcer diseases, while others have indicated that there is no such association.AIM: To examine the prevalence of antibodies to CagA and otherHelicobacter pyloriantigens in symptomatic and asymptomatic subjects in Turkey.SUBJECTS AND METHODS: Sixty-six symptomatic subjects, 16 to 74 years of age, were examined forH pyloriby biopsy-based tests and ELISA. One hundred nineteen asymptomatic subjects, 20 to 65 years of age, were also tested serologically for the presence ofH pylori. Samples from both groups that were found to be positive forH pyloriby ELISA were then tested by immunoblotting.RESULTS: Fifty-four (82%) symptomatic subjects and 76 (64%) asymptomatic subjects were found to beH pylori-positive by ELISA. Samples from 30 symptomatic subjects who were found to beH pylori-positive by ELISA were analyzed by immunoblotting. Antibodies to CagA (116 kDa) antigen were detected in immunoblots of 11 of 14 (79%) with chronic gastritis, 12 of 13 (92%) with duodenal ulcer and three of three (100%) with gastric cancer. Antigens of the following molecular weights were also detected in these 30 subjects: 89 kDa (VacA) in 21 (70%), 37 kDa in 21 (70%), 35 kDa in 19 (63%), 30 kDa in 27 (90%) and 19.5 kDa in 19 (63%). Immunoblots of 40 ELISA-positive asymptomatic subjects showed that 33 (83%) had antibodies to CagA antigen, 26 (65%) to VacA antigen, 30 (75%) to a 37 kDa antigen, 30 (75%) to a 35 kDa antigen, 39 (98%) to a 30 kDa antigen and 36 (90%) to a 19.5 kDa antigen.CONCLUSIONS: Antibodies to CagA antigen were prevalent in both groups, regardless of the presence of gastroduodenal disease.

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Helicobacter pylori VacA Targets Myeloid Cells in the Gastric Lamina Propria To Promote Peripherally Induced Regulatory T-Cell Differentiation and Persistent Infection

mBio ◽

10.1128/mbio.00261-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 9

Author(s):

Aleksandra Altobelli ◽

Michael Bauer ◽

Karelia Velez ◽

Timothy L. Cover ◽

Anne Müller

Keyword(s):

Helicobacter Pylori ◽

T Cell ◽

Persistent Infection ◽

Myeloid Cells ◽

T Cell Responses ◽

T Cell Differentiation ◽

Content Type ◽

Effector T Cell ◽

Cell Responses ◽

H Pylori

ABSTRACT The gastric bacterium Helicobacter pylori causes a persistent infection that is directly responsible for gastric ulcers and gastric cancer in some patients and protective against allergic and other immunological disorders in others. The two outcomes of the Helicobacter-host interaction can be modeled in mice that are infected as immunocompetent adults and as neonates, respectively. Here, we have investigated the contribution of the Helicobacter immunomodulator VacA to H. pylori-specific local and systemic immune responses in both models. We found that neonatally infected mice are colonized at higher levels than mice infected as adults and fail to generate effector T-cell responses to the bacteria; rather, T-cell responses in neonatally infected mice are skewed toward Foxp3-positive (Foxp3+) regulatory T cells that are neuropilin negative and express RORγt. We found these peripherally induced regulatory T cells (pTregs) to be enriched, in a VacA-dependent manner, not only in the gastric mucosa but also in the lungs of infected mice. Pulmonary pTreg accumulation was observed in mice that have been infected neonatally with wild-type H. pylori but not in mice that have been infected as adults or mice infected with a VacA null mutant. Finally, we traced VacA to gastric lamina propria myeloid cells and show that it suppressed interleukin-23 (IL-23) expression by dendritic cells and induced IL-10 and TGF-β expression in macrophages. Taken together, the results are consistent with the idea that H. pylori creates a tolerogenic environment through its immunomodulator VacA, which skews T-cell responses toward Tregs, favors H. pylori persistence, and affects immunity at distant sites. IMPORTANCE Helicobacter pylori has coexisted with humans for at least 60.000 years and has evolved persistence strategies that allow it to evade host immunity and colonize its host for life. The VacA protein is expressed by all H. pylori strains and is required for high-level persistent infection in experimental mouse models. Here, we show that VacA targets myeloid cells in the gastric mucosa to create a tolerogenic environment that facilitates regulatory T-cell differentiation, while suppressing effector T-cell priming and functionality. Tregs that are induced in the periphery during H. pylori infection can be found not only in the stomach but also in the lungs of infected mice, where they are likely to affect immune responses to allergens.

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