γδ T cells increase with gastric mucosal interleukin (IL)-7, IL-1β, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis

Background and Aims: The purpose of this study was to investigate possible factors that could impact on gamma delta T cell accumulation in the gastric mucosa. Method: Subjects were 22 Helicobacter pylori (H. pylori)-free and 75 H. pylori-infected mucosa biopsies classified into grades I similar to III gastritis as per our previous study. The number of gamma delta- and 45 RO-positive T cells were determined by immunostaining. Gastric mucosal anti-H. pylori urease specific antibodies and interleukin (IL)-1 beta, IL-2, 4, 7, 10 and IL-12 levels were assayed by enzyme-linked immunosorbent assay (ELISA). CC chemokine receptor 2 (CCR2) expression levels, migration, and cytokine production in gamma delta T cells stimulated by H. pylori urease were also evaluated. Results: The gamma delta T cell count was significantly higher in grade III gastritis which exhibits strong immunoglobulin (Ig)A and IgG responses to H. pylori urease with lymphoid follicles than in other groups. gamma delta T cell count was significantly correlated with IL-1 beta and interleukin-7 (IL-7) levels in the gastric mucosa. H. pylori urease immunoreactivity was detected in lamina propria of grade III gastritis, along with many gamma delta T cells. After H. pylori eradication therapy, the gamma delta T cell count in grade III gastritis significantly decreased. H. pylori urease stimulated significant increases in CCR2 expression levels, although to a lesser degree than those induced by IL-7 stimulation in both peripheral and mucosal gamma delta T cells. Interferon (IFN)-gamma and IL-10 production was also stimulated by H. pylori urease in peripheral gamma delta T cells. Conclusions: Gastric mucosal increases in IL-7 and IL-1 beta closely corresponded to the accumulation of gamma delta T cells in gastric mucosa. An association was also seen between gamma delta T cell accumulation and H. pylori urease-specific Ig levels.