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High Proportion of Granzyme B+ Intraepithelial Lymphocytes Contributes to Epithelial Apoptosis in Helicobacter pylori ‐Associated Lymphocytic Gastritis
Author(s) -
Han SongHee,
Joo Mee,
Kim KyoungMee
Publication year - 2013
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12042
Subject(s) - helicobacter pylori , granzyme b , gastritis , apoptosis , intraepithelial lymphocyte , immunology , granzyme , biology , medicine , cancer research , immune system , perforin , t cell , genetics , cd8
Abstract Background Helicobacter pylori infection has been linked to the development of lymphocytic gastritis ( LG ) characterized by ≥25 intraepithelial lymphocytes ( IEL s) per 100 epithelial cells. We hypothesize that the changes in the subpopulation and/or cytotoxicity of IEL s 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+ IEL s, the proportion of CD 8+ IEL s or TIA ‐1+ IEL s did not differ between two groups. The LG group showed a selective increase in GrB‐positive, phenotypically activated IEL s, which was paralleled by an increase in ApopTag indices. In contrast, the HPG group showed more heterogeneous IEL subpopulations with more CD 4+ IEL s and less GrB+ IEL s 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 IEL s, there are significant changes in the subpopulations and cytotoxicity of IEL s between HPG and H. pylori ‐associated LG . In particular, enhanced GrB‐associated cytotoxicity of the IEL s in H. pylori ‐associated LG contributes to an increase in epithelial apoptosis.