Immune modulation by regulatory T cells in Helicobacter pylori-associated diseases.
Regulatory T cells (Treg) have the ability to suppress the activity of most other lymphoid cells as well as dendritic cells through cell-cell contact dependent mechanisms, which have not yet been fully defined. Treg are a key component of a functional immune system, and Treg deficiency is associated with severe autoimmunity and allergies. Antigen-specific Treg accumulate in gastric tissue during both Helicobacter pylori-induced gastritis and peptic ulcer disease (PUD). Several studies suggest that the local Treg response protects the gastric mucosa from exaggerated inflammation and tissue damage, and the risk of PUD is inversely related to Treg frequencies. At the same time the reduction of the inflammatory response achieved by Treg leads to increased bacterial density. Furthermore, the inability to mount a protective inflammatory response will lead to chronic infection and in some patients to the development of atrophic gastritis and gastric cancer progression. Treg actively infiltrate gastric adenocarcinomas and are predicted to promote tumor escape from cytotoxic immune responses. In addition, the presence of a potent Treg response will probably be an obstacle when constructing a future therapeutic vaccine against H. pylori. In this article, we will review the proposed mechanisms of action for Treg, their accumulation in the gastric mucosa in the different H. pylori-associated diseases, and how they may affect the immune response induced by H. pylori infection and the course of PUD and gastric adenocarcinomas.
Department of Microbiology and Immunology, The Sahlgrenska Academy and the Center for Mucosal Immunobiology and Vaccines, University of Gothenburg, Gothenburg, Sweden.
Sukanya
S
Raghavan
Marianne
M
Quiding-Järbrink
D000230:Adenocarcinoma / Q000209:etiology / Q000276:immunology; D000818:Animals; D016481:Helicobacter Infections / Q000150:complications* / Q000453:epidemiology / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007109:Immunity / Q000502:physiology; D056747:Immunomodulation / Q000502:physiology*; D008954:Models, Biological; D013274:Stomach Neoplasms / Q000209:etiology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*