FOXP3+ Regulatory T Cells in Children with Helicobacter Pylori Infection

Abstract

Despite an intensive pro-inflammatory response, the immune system is unable to clear the organism in Helicobacter pylori gastritis. Regulatory T (Treg) cells, which suppress the immune response of antigen-specific T cells, have recently been demonstrated to play a key role in chronic inflammation by immunologic tolerance. The purpose of our study was to investigate the histopathology, FOXP3+CD4+CD25(high)Treg (FOXP3+Treg) cell expression, and immune responses in children with H. pylori infection. Twenty-four H. pylori -positive and 24 H. pylori -negative children who underwent esophagogastroduodenoscopy for dyspeptic symptoms were included. Histopathologic grading according to the updated Sydney classification and immunohistochemical stains for FOXP3, transforming growth factor-β1 (TGF-β1), and CD4 were performed. Histopathologic bacterial density score, gastritis activity score, and chronic inflammation score were higher in the H. pylori -positive group than in the negative group (P < 0.01). The number of FOXP3+Treg cells and CD4+T cells and the grade of TGF-β1 expression were significantly increased in the H. pylori -positive group compared to the negative group (P < 0.01). The number of FOXP3+Treg cells correlated positively with the grade of TGF-β1 expression regardless of H. pylori status (P < 0.05). The number of FOXP3+Treg cells and the grade of TGF-β1 expression correlated positively with H. pylori density, gastritis activity score, and chronic inflammation score regardless of H. pylori status (P < 0.01). These findings indicate that FOXP3+Treg cells could play a role in persistent H. pylori infection.

Role of childhood infection in the sequelae of H. pylori disease

“…13 The increased gastric Treg response in infected children exceeded that of uninfected children. 13,14,105 These findings confirm the identification of Treg cells in human gastric mucosa by other investigators [106][107][108] and indicate that the reduced gastric inflammation of H. pyloriinfected children is strongly associated with enhanced mucosal Treg activity.…”

Helicobacter pylori Cytotoxin-Associated Gene A Impairs Human Dendritic Cell Maturation and Function through IL-10–Mediated Activation of STAT3

“…Several lines of evidence suggest that H. pylori may induce a response by Tregs, leading to H. pylori persistence. In this regard, the expression levels of the Treg marker Foxp3 have been described to be higher in the gastric epithelium of H. pyloriinfected subjects (4)(5)(6)(7)(8). In addition, chronic exposure of murine DCs to H. pylori has been reported to have a detrimental effect on the ability of DCs to induce a Th1 response (9).…”

Inflammation, Immunity, and Vaccines for Helicobacter pylori Infection

“…In the clinical setting, Tregs were shown to be increased in a cohort of H. pylori-infected children, where the number of FoxP3-expressing cells and the level of TGF-b present in the gastric mucosa were positively correlated with the density of H. pylori [19].…”

“…In the clinical setting, Tregs were shown to be increased in a cohort of H. pylori -infected children, where the number of FoxP3 expressing cells and the level of TGF-β present in the gastric mucosa was positively correlated with the density of H. pylori (19). Another study further confirmed a predominate Treg response in children, and further showed that infection in children induces less Th17 than in adults (20).…”