CCR6+ T helper cells and regulatory T cells in the blood and gastric mucosa during Helicobacter pylori infection

Background

Helicobacter pylori (H. pylori) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of H. pylori bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote H. pylori persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6⁺ Th cells and CCR6⁺ Tregs during H. pylori infection in humans.

Materials and Methods

Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4⁺ and CD4⁺CCR6⁺CD45RO⁺ T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4⁺CD25^hiFoxP3⁺ Tregs and various groups of Th cells.

Results

CD4⁺CCR6⁺ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6⁺ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4⁺CCR6⁺CD45RO⁺ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori-positive patients, circulating CD4⁺CCR6⁺ cells contained a higher proportion of H. pylori-specific cells compared with their CD4⁺CCR6⁻ counterparts. H. pylori infection strongly increased the content of CD4⁺ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4⁺ lymphocytes expressing CCR6. CD4⁺CCR6⁺ lymphocytes from H. pylori-infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation.

Conclusion

H. pylori infection causes an increase in the number of mature CD4⁺CCR6⁺ lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4⁺CCR6⁺ lymphocytes, including CCR6⁺ Th1 cells and Tregs.