High Proportion of Granzyme B-Positive (Activated) Intraepithelial and Lamina Propria Lymphocytes in Lymphocytic Gastritis

Oberhuber, Georg; Bodingbauer, Martin; Mosberger, Isabella; Stolte, Manfred; Vogelsang, Harald

doi:10.1097/00000478-199804000-00010

Cited by 88 publications

(58 citation statements)

References 28 publications

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“…10 TIA-1 is expressed in both resting and activated cytotoxic T-cells, whereas granzyme B is a marker of activated cytotoxic T-cells. 7 Intraepithelial CD4+ IELs and CD8+ resting cytotoxic T-cells characterized LG in the present case. Regulatory T-cells commonly express CD4, CD25 and FoxP3.…”

supporting

confidence: 53%

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Lymphocytic gastritis showing concomitant occurrence of both CD4 + and CD8 + T‐cells among epithelial cells

Fujiwara

Akatsuka

et al. 2014

Pathology International

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supporting

confidence: 53%

“…6 Intraepithelial lymphocytes in LG belong to T-cells, express CD8+, and are mostly positive for granzyme B, being categorized in activated cytotoxic T-cells. 7 Expression of CD4 on IELs is an exceptional event. 8 We briefly report herein a case of unique LG showing concomitant occurrence of both CD4 + and CD8 + T-cells among the epithelia.…”

mentioning

confidence: 99%

Lymphocytic gastritis showing concomitant occurrence of both CD4 + and CD8 + T‐cells among epithelial cells

Fujiwara

Akatsuka

et al. 2014

Pathology International

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“…Lymphocytes with this phenotype represent the predominant intraepithelial lymphocyte population of normal human small intestinal mucosa 40,41 and expansions of this subset have been described in giardiasis. 42 In contrast, duodenal intraepithelial lymphocytes in celiac disease 42 as well as gastric intraepithelial lymphocytes in celiac disease-associated lymphocytic gastritis 43 have an 'activated' cytotoxic phenotype, that is, the intraepithelial lymphocytes express perforin and granzyme-B. The presence of activated cytotoxic T cells has been documented in the gastric lamina propria in H. pylori gastritis and some cases of NSAIDinduced acute gastritis 43,44 but we are not aware of any studies that have demonstrated this phenotype of the intraepithelial lymphocytes in H. pyloriassociated lymphocytic gastritis.…”

Section: Discussionmentioning

confidence: 99%

Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis

et al. 2005

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We have observed expansions of intraepithelial lymphocytes in duodenal biopsies from patients with Helicobacter pylori gastritis. This study was undertaken to prospectively evaluate, unselected, paired gastric and duodenal biopsies from 50 patients with H. pylori gastritis and a comparison group of 30 patients with other types of gastritis (10 autoimmune and 20 reactive) to: (1) quantify duodenal intraepithelial lymphocytes, determine their distribution patterns, epithelial location, and phenotype, and (2) correlate the intraepithelial lymphocyte elevations with various features of gastric and duodenal pathology. Intraepithelial lymphocytes were analyzed with antibodies including CD3, CD8, and TIA-1. A stain for H. pylori was performed on all gastric and duodenal biopsies. Duodenal intraepithelial lymphocytes from patients with H. pylori gastritis (using CD3) ranged from 3 to 42 lymphocytes/100 epithelial cells (mean 18.5) compared to 3 to 18 lymphocytes/100 epithelial cells (mean 6.6) in the comparison group. Intraepithelial lymphocyte elevations were seen in 44% of the duodenal biopsies from patients with H. pylori gastritis (using CD3). Significant differences in the intraepithelial lymphocyte counts between patients with H. pylori gastritis and the comparison group were seen for all three T-cell antigens (Po0.001 for CD3 and CD8 and Po0.002 for TIA-1). Duodenal intraepithelial lymphocytes in the H. pylori þ cases had a latent cytotoxic phenotype, H. pylori was not visualized in any of the duodenal biopsies from patients with H. pylori gastritis, and no patient had clinical evidence of celiac disease. Our study highlights frequent duodenal intraepithelial lymphocytosis in individuals with H. pylori gastritis and the lymphocyte distribution patterns (and numbers) overlapped with those described for celiac disease patients. H. pylori gastritis must be considered as a possible explanation for duodenal intraepithelial lymphocytosis with normal villous architecture, especially when lymphocytosis is patchy, intraepithelial lymphocytes display a 'latent' cytotoxic phenotype, and the clinical findings and serologic profile does not fit celiac disease.

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“…Interestingly, hsp60 stimulation induced â 7 integrin in PBMC mRNA from patients with MALT lymphoma. Intraepithelial and lamina propria lymphocytes in H. pylori-positive gastric mucosa expressed granzyme B at high levels (Oberhuber et al, 1998). The function of granzyme B involves CD8 þ T-cell differentiation, specialization and regulation (Sandberg et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma

Yamasaki

Yokota

Okada

et al. 2004

Journal of Medical Microbiology

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We have reported previously that heat-shock protein 60 kDa (hsp60) of Helicobacter pylori is an important antigen in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In order to investigate associations with host immune reactions and hsp60 antigen, CD40 ligand (CD40L) expression and cytokine production were analysed following stimulation with hsp60. To provide a clear antigen-driven immune response, peripheral blood mononuclear cells (PBMC) from patients with low-grade MALT lymphoma and gastritis and those from healthy volunteers were stimulated with recombinant H. pylori hsp60 and H. pylori cell lysate in the presence of cytokines (IL4 and granulocyte-macrophage colony-stimulating factor). mRNA expression was also analysed by a cDNA microarray containing 1100 genes. Expression of CD40L on PBMCs of patients with MALT lymphoma was increased by cytokines or by combination with stimulation with hsp60 antigens. The production of IL4 in PBMC cultures was increased in patients with MALT lymphoma; however, production of IFN-ª was at low levels. DNA microarray analysis indicated increased levels of HLA-DR and integrin mRNAs. In cases of low-grade MALT lymphoma, adaptive immune responses against hsp60 may be enhanced by host factors, such as antigen presentation and T-cell activation, resulting in B-cell proliferation, which can be demonstrated during chronic H. pylori infection. INTRODUCTIONA close link between Helicobacter pylori infection and the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has been established in some studies. H. pylori infection has been confirmed in most cases of MALT lymphoma Parsonnet et al., 1994;Wotherspoon et al., 1991 Wotherspoon et al., , 1993. Low-grade MALT lymphomas often regress following the eradication of H. pylori (Bayerdorffer et al., 1995), and they relapse with re-infection with H. pylori (Cammarota et al., 1995;Horstmann et al., 1994).Heat-shock protein (hsp) is a candidate cross-reacting antigen in microbial infections. Our previous studies have shown that hsp60 is expressed in follicular dendritic cells (FDC) of gastric lymphoid tissues in patients with gastric MALT lymphoma (Kobayashi et al., 1998), and antibodies to human hsp60 have been detected in patients with MALT lymphoma (Kawahara et al., 1999). These results indicate that hsp60 may be associated with the host immune reaction in cases of H. pylori infection and, more specifically, with B-cell proliferation in the gastric mucosa of patients with MALT lymphoma. Some reports have indicated that the proliferation and differentiation of MALT lymphoma tumour cells depends on H. pylori-antigen-specific T cells, as well as on the co-stimulatory signal of the CD40 ligand (CD40L) on CD4 þ helper T cells and on the cytokines associated with the T helper 2 (Th-2)-type response (Greiner et al., 1998;Hussell et al., 1993Hussell et al., , 1996Knorr et al., 1999 revolutionized the analysis of gene expression profiles. A DNA microarray can contain thousands of cDNAs or oligonuc...

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High Proportion of Granzyme B-Positive (Activated) Intraepithelial and Lamina Propria Lymphocytes in Lymphocytic Gastritis

Cited by 88 publications

References 28 publications

Lymphocytic gastritis showing concomitant occurrence of both CD4 + and CD8 + T‐cells among epithelial cells

Lymphocytic gastritis showing concomitant occurrence of both CD4 + and CD8 + T‐cells among epithelial cells

Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis

Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma

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