scholarly journals Expression of the Programmed Death Ligand 1, B7-H1, on Gastric Epithelial Cells after Helicobacter pylori Exposure Promotes Development of CD4+ CD25+ FoxP3+ Regulatory T Cells

2007 ◽  
Vol 75 (9) ◽  
pp. 4334-4341 ◽  
Author(s):  
Ellen J. Beswick ◽  
Irina V. Pinchuk ◽  
Soumita Das ◽  
Don W. Powell ◽  
Victor E. Reyes
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Treg Cells ◽  
T Cell Response ◽  
Gastric Epithelium ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT During Helicobacter pylori infection, T cells are recruited to the gastric mucosa, but the host T-cell response is not sufficient to clear the infection. Some of the recruited T cells respond in a polarized manner to a Th1 response, while others become anergic. We have previously shown that T-cell anergy may be induced during infection by the interaction of T cells with B7-H1, which is up-regulated on the gastric epithelium during H. pylori infection. Recently, regulatory T (Treg) cells with a CD4+ CD25high FoxP3+ phenotype were found at an increased frequency in the gastric mucosa of biopsy specimens from H. pylori-infected patients. While Treg cells are important in maintaining tolerance, they can also suppress immune responses during infection. In this study, we examined the induction of the Treg phenotype when naïve T cells were incubated with gastric epithelial cells exposed to H. pylori. The frequency of this phenotype was markedly decreased when B7-H1 was blocked with monoclonal antibodies or its expression was blocked with small interfering RNA. The functional role of these Treg cells was assessed in proliferation assays when the cells were cocultured with activated T cells, which effectively decreased proliferation of the cells.

scholarly journals Helicobacter pylori Elicits B7-H3 Expression on Gastric Epithelial Cells: Implications in Local T Cell Regulation and Subset Development During Infection

2019 ◽  
pp. 1-12
Author(s):  
Taslima T. Lina ◽  
Jazmin Gonzalez ◽  
Irina V. Pinchuk ◽  
Ellen J. Beswick ◽  
Victor E. Reyes
Keyword(s):  
Helicobacter Pylori ◽  
T Cell ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Th17 Cells ◽  
Treg Cells ◽  
Gastric Epithelial Cells ◽  
Th2 Response ◽  
Th2 Responses ◽  
H Pylori

Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects more than 50% of humanity and is associated with gastritis, peptic ulcer and gastric cancer. Although CD4+ T cells are recruited to the gastric mucosa, the host is unable to clear the bacteria. Previously, we demonstrated that H. pylori infection upregulates the expression of the T cell co-inhibitory molecule B7-H1 while simultaneously downregulating the expression of T cell co-stimulatory molecule B7-H2 on gastric epithelial cells (GEC), which together affect the Treg and Th17 cell balance and foster bacterial persistence. Because B7-H3, another member of the B7 family of co-inhibitory receptors, has been found to have important immunoregulatory roles and in cancer, in this study we examined the expression of B7-H3 molecules on GEC and how the expression is regulated by H. pylori during infection. Our study showed that both human and murine GEC constitutively express B7-H3 molecules, but their expression levels increased during H. pylori infection. We further demonstrated that H. pylori uses its type 4 secretion system (T4SS) components CagA and cell wall peptidoglycan (PG) fragment to upregulate B7-H3. Th17 cells and Treg cells which are increased during H. pylori infection also had an effect on B7-H3 induction. The underlying cell signaling pathway involves modulation of p38MAPK pathway. Since B7-H3 were shown to up-regulate Th2 responses, the phenotype of T cell subpopulations in mice infected with H. pylori PMSS1 (contains functional T4SS) or SS1 (cannot deliver CagA into GEC) strains were characterized. A mixed Th1/Th2 response in H. pylori infected mice was observed. Consistent with previous findings, increased Treg cells and decreased Th17 cells in MLN of PMSS1 infected mice compared to SS1 infected mice was observed. Human biopsy samples collected from gastritis biopsies and gastric tumors showed a strong association between increased B7-H3 and Th2 responses in H. pylori strains associated with gastritis. T cell: GEC co-cultures and anti-B7-H3 blocking Ab confirmed that the induction of Th2 is mediated by B7-H3 and associated exclusively with an H. pylori gastritis strain not cancer or ulcer strains. In conclusion, these studies revealed a novel regulatory mechanism employed by H. pylori to influence the type of T cell response that develops within the infected gastric mucosa.

Intrafamilial Infection of Helicobacter Pylori: Abnormal Gastric Epithelial Cells, Pedestal-Rich H. Pylori Adherence, and a Gene Mutation in a Child with Protein-Losing Gastroenteropathy

2019 ◽  
Vol 2 (3) ◽  
pp. 83-99
Author(s):  
T.W. Wan ◽  
O. Khokhlova ◽  
W. Higuchi ◽  
I. Protasova ◽  
Olga V. Peryanova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Gene Mutation ◽  
Virulence Factor ◽  
East Asian ◽  
Gastric Epithelium ◽  
Gastric Epithelial Cells ◽  
H Pylori

Abstract Helicobacter pylori, one of the most prevalent human pathogens, colonizes the gastric mucosa and is associated with gastric diseases, such as gastritis and peptic ulcers, and is also a bacterial risk factor for gastric cancer. Cytotoxin-associated gene A (CagA) protein, a major virulence factor of H. pylori, is phosphorylated in cells at its Glu-Pro-IIe-Tyr-Ala (EPIYA) motif and is considered to trigger gastric cancer. CagA is classified into two forms, Western CagA with EPIYA-ABC and East Asian CagA with EPIYA-ABD, with the latter associated with a high risk of developing gastric cancer. CagA causes morphological transformation of cells, yielding the “hummingbird” phenotype in AGS cells and possibly membranous pedestals in the gastric epithelium, albeit rarely. H. pylori adherence to the gastric mucosa is not yet fully understood. Here, we describe an intrafamilial infection case of H. pylori, focusing on the gastric epithelium, H. pylori adherence, and a gene mutation in a child with protein-losing gastroenteropathy (characterized by excessive loss of plasma proteins into the gastrointestinal tract). H. pylori, which also infected family members (mother and father), was genetically a single clone with the virulence genes of an East Asian type. The patient’ gastric mucosa exhibited some unique features. Endoscopy revealed the presence of protein plugs on the mucosal surface, which were immunoelectrophoretically similar to serum proteins. Electron microscopy revealed abnormal gastric epithelial cells, totally covered with the secretions or possessing small swollen structures and irregular microvilli. The patient’s H. pylori infection was characterized by frequently occurring thick pedestals, formed along adherent H. pylori. The serum protein level returned to normal and the protein plugs disappeared after the successful eradication of H. pylori, albeit with lag periods for healing. He had a mutation in the OCRL1 gene, associated with Dent disease (asymptomatic proteinuria). Thus, in the patient’s gastric mucosa, we found the abnormal gastric epithelial cells, which may be caused by an OCRL1 mutation or H. pylori, and pedestal-rich H. pylori infection, possibly caused by a higher level of action of CagA in the abnormal epithelial cells. The data suggests a novel H. pylori virulence factor associated with “excessive plasma protein release”.

scholarly journals Helicobacter pylori-induced adrenomedullin modulates IFN-γ-producing T-cell responses and contribute to gastritis

2018 ◽  
Author(s):  
Hui Kong ◽  
Jin-yu Zhang ◽  
Fang-yuan Mao ◽  
Yong-sheng Teng ◽  
Yi-pin Lv ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
T Cell Responses ◽  
Dependent Manner ◽  
Gastric Epithelial Cells ◽  
Cell Responses ◽  
Ifn Γ ◽  
H Pylori

AbstractAdrenomedullin (ADM) is a multifunctional peptide that is expressed by many surface epithelial cells, but its relevance to H. pylori-induced gastritis is unknown. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice. In H. pylori-infected human gastric mucosa, ADM expression was positively correlated with the degree of gastritis, accordingly, blockade of ADM resulted in decreased inflammation within the gastric mucosa of H. pylori-infected mice. During H. pylori infection, ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner, and resulted in increased inflammation within the gastric mucosa. This inflammation was characterized by the increased IFN-γ-producing T cells, whose differentiation was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses, thereby contributing to the development of H. pylori-associated gastritis. Accordingly, blockade of IFN-γ or knockout of IFN-γ decreased inflammation within the gastric mucosa of H. pylori-infected mice. This study identifies a novel regulatory network involving H. pylori, gastric epithelial cells, ADM, macrophages, T cells, and IFN-γ, which collectively exert a pro-inflammatory effect within the gastric microenvironment.Author summaryH. pylori infect almost half the world’s population. Once infected, most of people carry the bacteria lifelong if left untreated, so that persistent H. pylori infection can lead to chronic gastritis, peptic ulceration and ultimately gastric cancer. H. pylori infection is accompanied with increased inflammation in gastric mucosa, but the mechanisms of chronic gastritis induced by H. pylori infection remains poorly understood. We studied a multifunctional peptide known as adrenomedullin (ADM) in gastric epithelial cells, which was known as a key factor of regulating gastrointestinal physiology and pathology. Here, we found that gastric ADM expression was elevated in gastric mucosa of H. pylori-infected patients and mice, and was positively correlated with the degree of gastritis. ADM production was promoted via PI3K-AKT signaling pathway activation by gastric epithelial cells in a cagA-dependent manner. Blockade of ADM during H. pylori infection resulted in decreased gastric inflammation that was characterized by the increased IFN-γ-producing T cells which was induced via the phosphorylation of AKT and STAT3 by ADM derived from gastric epithelial cells. ADM also induced macrophages to produce IL-12, which promoted the IFN-γ-producing T-cell responses. These data demonstrate that H. pylori-induced ADM modulates FN-γ-producing T-cell responses and contribute to gastritis.

scholarly journals Mechanisms of interacting Helicobacter pylori with gastric mucosal epithelium. II. A reaction of gastric epithelium on Helicobacter pylori colonization and persistence

2019 ◽  
Vol 9 (2) ◽  
pp. 253-261
Author(s):  
O. K. Pozdeev ◽  
A. O. Pozdeeva ◽  
Yu. V. Valeeva ◽  
P. E. Gulyaev ◽  
A. N. Savinova
Keyword(s):  
Helicobacter Pylori ◽  
T Cell ◽  
Epithelial Cell ◽  
Gastric Mucosa ◽  
Mapk Pathway ◽  
Bacterial Colonization ◽  
Gastric Epithelium ◽  
T Cell Subsets ◽  
H Pylori ◽  
Apoptotic Factors

Gastric and duodenal recurrent inflammatory diseases have a high prevalence, but the role played by microbes in its development remained unclear. However, the data published in 1983 by Marshall and Warren about isolatingHelicobacter pylorifrom the stomach mucosa of the patient with gastritis and proposing relevant cultivation methods was the turning point in investigating etiology of the upper digestive tract inflammatory disorders. Moreover, it was shown that the majority ofH. pylorispp. are found within the gastric lumen upon colonization, whereas around 20% of them are attached to the epithelial cells in the stomach. In addition, effects of interacting H. pylori with gastric epithelium and activation of some defense mechanisms due to bacterial colonization and spreading were analyzed. It was found that along with triggering pro-inflammatory response induced by proteins VacA as well as phosphorylated/unphosphorylated CagA, wherein the latter is able to induce a set of protective reactionsH. pyloridisrupts intercellular contacts, affects epithelial cell polarity and proliferation, and activates SHP-2 phosphatase resulting in emerging diverse types of cellular responses. The activation mechanisms for the mitogen-activated protein kinase (MAPK) pathway were discussed. The ability ofH. pylorito regulate apoptosis, particularly via its suppression, by expressing ERK kinase and protein MCL1 facilitating bacterial survival in the gastric mucosa as well as beneficial effects related to bacterial circulation on gastric epithelial cell survival elicited by anti-apoptotic factors were also examined. Of note, persistence of H. pylori are mainly determined by activating transcriptional factors including NF-κB, NFAT, SRF, T-cell lymphoid enhancing factor (TCF/LEF), regulating activity of MCL1 protein, in turn, being one of the main anti-apoptotic factors, as well as induced production of the migration inhibitory factor (MIF). The role of VacA cytotoxin in triggering epithelial cell apoptosis via caspase-mediated pathways was also considered. Infection withH. pyloriis accompanied by release of proinflammatory cytokine cocktail detected bothin vitroandin vivo. In particular, bacterial urease activating transcriptional factor NF-κB was shown to play a crucial role in inducing cytokine production. Moreover, such signaling pathways may be activated afterH. pyloriis attached to the cognate receptor in the gastric epithelial surface by interacting with CD74 and MHC class II molecules. Finally, a role for various CD4+T cell subsets, particularly type 17 T helper cells (Th17) in inducing immune response against H. pylori antigens in gastric mucosa was revealed were also discussed. 

Aberrant CpG Island Hypermethylation in Pediatric Gastric Mucosa in Association With Helicobacter pylori Infection

2011 ◽  
Vol 135 (6) ◽  
pp. 759-765
Author(s):  
So-Hyun Shin ◽  
Seog-Yun Park ◽  
Jae-Sung Ko ◽  
Nayoung Kim ◽  
Gyeong Hoon Kang
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Cpg Island ◽  
Methylation Status ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelial Cells ◽  
Infected Adult ◽  
H Pylori ◽  
Methylight Assay

Abstract Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion. Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues. Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples. Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P < .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P < .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P < .05). Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.

scholarly journals Helicobacter pylori Induces RANTES through Activation of NF-κB

2003 ◽  
Vol 71 (7) ◽  
pp. 3748-3756 ◽  
Author(s):  
Naoki Mori ◽  
Alan M. Krensky ◽  
Romas Geleziunas ◽  
Akihiro Wada ◽  
Toshiya Hirayama ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Intracellular Signaling ◽  
Interleukin 1 ◽  
Luciferase Reporter ◽  
Transcriptional Level ◽  
Gastric Epithelial Cells ◽  
Rantes Promoter ◽  
H Pylori

ABSTRACT Helicobacter pylori-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells and neutrophils. RANTES (short for “regulated upon activation, normal T cell expressed and secreted”) is a chemoattractant cytokine (chemokine) important in the infiltration of T lymphocytes and monocytes. RANTES may therefore contribute to the cellular infiltrate in the H. pylori-infected gastric mucosa. The aim of this study was to analyze the molecular mechanism responsible for H. pylori-mediated RANTES expression. We observed that gastric epithelial cells produced RANTES upon coculture with H. pylori. In addition, H. pylori induced RANTES mRNA expression and an increase in luciferase activity in cells which were transfected with a luciferase reporter construct derived from the RANTES promoter, in gastric epithelial cells, indicating that the induction of RANTES production occurred at the transcriptional level. Induction of RANTES was dependent on an intact cag pathogenicity island. Activation of the RANTES promoter by H. pylori occurred through the action of NF-κB. Transfection of kinase-deficient mutants of IκB kinase (IKK) and NF-κB-inducing kinase (NIK) inhibited H. pylori-mediated RANTES activation. In contrast, tumor necrosis factor alpha- or interleukin-1/Toll-like receptor signaling molecules—such as mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1, MyD88, and interleukin-1 receptor-associated kinase—did not play a role in RANTES activation by H. pylori. Collectively, H. pylori induced NF-κB activation through an intracellular signaling pathway that involved IKK and NIK, leading to RANTES gene transcription. RANTES induction by H. pylori may play an important role in gastric inflammation.

Human Gastric Epithelium Produces IL-4 and IL-4δ2 Isoform Only upon Helicobacter Pylori Infection

2007 ◽  
Vol 20 (4) ◽  
pp. 809-818 ◽  
Author(s):  
B. Orsini ◽  
J.R. Vivas ◽  
B. Ottanelli ◽  
A. Amedei ◽  
E. Surrenti ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Healthy Subjects ◽  
Fine Tuning ◽  
Gastric Epithelium ◽  
Gastric Epithelial Cells ◽  
H Pylori ◽  
Cag Pai

Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4δ2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island ( cag-PAI). IL-4 and IL-4δ2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SSI strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori-infected patients, and markedly reduced in cag-PAI-positive ones. IL-4δ2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-452 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SSI strain stimulation, whereas IL-4δ2 mRNA expression was detected in AGS co-cultured with either SSI or B128 strains. An inverse correlation was documented between IL-4 and IL-482 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-452, is expressed by gastric epithelium of healthy subjects, whereas IL-452 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4δ2 expression.

scholarly journals Helicobacter pylori Binds to CD74 on Gastric Epithelial Cells and Stimulates Interleukin-8 Production

2005 ◽  
Vol 73 (5) ◽  
pp. 2736-2743 ◽  
Author(s):  
Ellen J. Beswick ◽  
David A. Bland ◽  
Giovanni Suarez ◽  
Carlos A. Barrera ◽  
Xuejung Fan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Surface Expression ◽  
Class Ii ◽  
Gastric Epithelium ◽  
Host Responses ◽  
Gastric Epithelial Cells ◽  
Class Ii Mhc ◽  
H Pylori

ABSTRACT The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-γ) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.

scholarly journals Helicobacter pylori Infection Induces Interleukin-8 Receptor Expression in the Human Gastric Epithelium

2003 ◽  
Vol 71 (6) ◽  
pp. 3357-3360 ◽  
Author(s):  
Fredrik Bäckhed ◽  
Elisabeth Torstensson ◽  
Delphine Seguin ◽  
Agneta Richter-Dahlfors ◽  
Bachra Rokbi
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Gastric Biopsy ◽  
Receptor Expression ◽  
Interleukin 8 ◽  
Gastric Epithelium ◽  
Epithelial Cell Line ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT The gastric pathogen Helicobacter pylori is known to activate multiple proinflammatory signaling pathways in epithelial cells. In this study, we addressed the question of whether expression of the interleukin-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) is upregulated in H. pylori-infected human gastric biopsy samples. Biopsy samples from patients infected with H. pylori strains harboring the cag pathogenicity island (PAI) expressed larger amounts of both receptors. In addition, IL-8RB expression was induced in the gastric epithelial cell line AGS upon infection with a clinical isolate containing the cag PAI, while a strain lacking the cag PAI did not. Our finding suggests that gastric epithelial cells express IL-8R in response to H. pylori infection.

scholarly journals Helicobacter pylori Induces Transendothelial Migration of Activated Memory T Cells

2005 ◽  
Vol 73 (2) ◽  
pp. 761-769 ◽  
Author(s):  
Karin Enarsson ◽  
Mikael Brisslert ◽  
Steffen Backert ◽  
Marianne Quiding-Järbrink
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Gastric Mucosa ◽  
Memory T Cells ◽  
Umbilical Vein ◽  
Transendothelial Migration ◽  
Ulcer Disease ◽  
H Pylori

ABSTRACT Helicobacter pylori infection is associated with pronounced infiltration of granulocytes and lymphocytes into the gastric mucosa, resulting in active chronic gastritis that may develop into duodenal ulcer disease or gastric adenocarcinoma. Infiltrating T cells play a major role in the pathology of these diseases, but the signals involved in recruitment of T cells from blood to H. pylori-infected tissues are not well understood. We therefore examined H. pylori-induced T-cell transendothelial migration (TEM). The Transwell system, employing a monolayer of human umbilical vein endothelial cells, was used as a model to study TEM. H. pylori induced a significant T-cell migration, compared to spontaneous migration. CD4+ and CD8+ T cells migrated to the same extent in response to H. pylori, whereas there was significantly larger transmigration of memory T cells compared to naive T cells. Both H. pylori culture filtrate and urease induced migration, and the presence of the H. pylori cag pathogenicity island increased TEM. T-cell TEM was mediated by LFA-1-ICAM-1 interactions in accordance with an increased ICAM-1 expression on the endothelial cells after contact with H. pylori. Migrating T cells had increased expression of activation marker CD69 and chemokine receptors CXCR3, CCR4, and CCR9. Furthermore, T cells migrating in response to H. pylori secreted Th1 but not Th2 cytokines upon stimulation. In conclusion, our data indicate that live H. pylori and its secreted products contribute to T-cell recruitment to the gastric mucosa and that the responding T cells have an activated memory Th1 phenotype.

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