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Helicobacter. 2013 Aug;18(4):290-8. doi: 10.1111/hel.12042. Epub 2013 Jan 29.

High proportion of granzyme B+ intraepithelial lymphocytes contributes to epithelial apoptosis in Helicobacter pylori-associated lymphocytic gastritis.

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1
Department of Pathology, Inje University Ilsan Paik Hospital, 2240 Daehwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 411-706, South Korea.

Abstract

BACKGROUND:

Helicobacter pylori infection has been linked to the development of lymphocytic gastritis (LG) characterized by ≥25 intraepithelial lymphocytes (IELs) per 100 epithelial cells. We hypothesize that the changes in the subpopulation and/or cytotoxicity of IELs leading to epithelial cell apoptosis may be involved in the pathogenesis of H. pylori-associated LG.

MATERIALS AND METHODS:

We examined IEL subpopulations and the expression of cytotoxic molecules by IELs in biopsy specimens from 36 patients with H. pylori-associated LG by immunostainings for CD3, CD4, CD8, T-cell-restricted intracellular antigen-1 (TIA-1), and granzyme B (GrB) and compared the results with those obtained from 49 patients with H. pylori-associated gastritis (HPG). To investigate whether the IEL-mediated cytotoxicity is related to the increase of epithelial apoptosis, we performed a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay using ApopTag detection kit.

RESULTS:

Between LG and HPG groups, significant differences in the number of CD3+, CD4+, CD8+, TIA-1+ or GrB+ IELs, and ApopTag indices were found. Among the CD3+ IELs, the proportion of CD8+ IELs or TIA-1+ IELs did not differ between two groups. The LG group showed a selective increase in GrB-positive, phenotypically activated IELs, which was paralleled by an increase in ApopTag indices. In contrast, the HPG group showed more heterogeneous IEL subpopulations with more CD4+ IELs and less GrB+ IELs compared with the LG group, and we did not find any significant variable contributing to the epithelial apoptosis in the HPG group.

CONCLUSIONS:

This study shows that in addition to the numerical increase in the IELs, there are significant changes in the subpopulations and cytotoxicity of IELs between HPG and H. pylori-associated LG. In particular, enhanced GrB-associated cytotoxicity of the IELs in H. pylori-associated LG contributes to an increase in epithelial apoptosis.

PMID:
23356909
DOI:
10.1111/hel.12042
[Indexed for MEDLINE]
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