Immune Modulation by Regulatory T Cells in Helicobacter pylori-Associated Diseases

Abstract

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.

Complex T Cell Interactions Contribute to Helicobacter pylori Gastritis in Mice

“…It has become clear that hosts that mount a strong proinflammatory response are more likely to develop severe complications of disease, such as peptic ulcers or neoplasia (17), although the factors that determine which hosts will develop such responses remain unclear. In fact, the most recent evidence suggests that in humans, the primary response to infection is actually immunoregulatory (18)(19)(20)(21)(22). This finding supports many years of animal research indicating that suppression of regulatory responses is necessary for induction of severe disease (11,(23)(24)(25)(26)(27)(28)(29)(30)(31).…”

“…Carriage of the cag pathogenicity island by the infecting strain clearly exacerbates disease in some cases (6), but evidence is mounting to indicate that the overall outcome of disease is heavily dependent on the host immune response. Interestingly, most hosts, whether they are experimental animals or infected humans, respond minimally to gastric colonization by H. pylori, and it is the exception among humans and the manipulated models among animals that develop severe disease (17,18). It has become clear that hosts that mount a strong proinflammatory response are more likely to develop severe complications of disease, such as peptic ulcers or neoplasia (17), although the factors that determine which hosts will develop such responses remain unclear.…”

Influence exerted by helicobacter pylori on regulatory t-cells differentiation

“…There are some mechanisms which favor long persistence of H. pylori in a host; increased CD4+CD25+FoxP3+ Т-regulatory cells content which can at least be observed at later contamination stages is one of them [9]. T-regulatory cells (T-reg) are a specialized subpopulation of CD4+ T-lymphocytes which is able to suppress activity of other lymphoid cells and either prevent or decrease intensity of inborn and adaptive immune response.…”

<italic>Helicobacter pylori </italic>Infection: Regulatory T Cells and Their Participation in the Immune Response

“…Other studies agree with these results and show an inverse relationship between the risk of peptic ulcer disease and the frequency of regulatory T cells. Even, indicate that the reduction of Treg increases bacterial colonization (45). The induction of Tregs by H. pylori may prove to be a major adaptation to evade host immunity.…”

“…The bacterium is able to stimulate DCs to prime Tregs and the functional significance of H. pylori-induced Treg response is the restriction of Th17 priming. Inhibition of Th17 immunity may allow chronic persistence of the bacteria (59), Researchers (45) indicate that the potent Treg response may affect the development of vaccine against H. pylori.…”