The Helicobacter pylori-induced regulatory T-cell response

The bacterium (germ) Helicobacter pylori is the main cause of stomach and duodenal ulcers and of stomach cancer. The bacterium is common, but most people who have it never develop either of these conditions and stay entirely well. The infection induces an immune response but this does not usually kill the bacteria, which may persist in the stomach lining for life unless antibiotics are administered. Published data suggest that differences in the type of immune response to H. pylori could protect against or favour the development of ulcers and gastric cancer. Our recent research indicates that immune cells of a suppressive nature (regulatory T-cells) may help to prevent ulceration by reducing inflammation, and these cells might also help the bacteria to remain in the stomach. Our experiments showed that people with peptic ulcers have low levels of regulatory T-cells, and this possibly means that there are insufficient numbers of these cells to prevent the development of severe inflammation of the stomach lining. We now need to prove if reducing the regulatory T-cell response does change the amount of inflammation, by infecting mice and giving a treatment to block their suppressive activity. It is important for us to know more about these suppressive T-cells, how they act, and what induces their production during the immune response. If we have a good understanding of this, we may be able to identify those at risk of developing disease in the future and design effective vaccines. If the work is successful we plan to make the results widely available. Both the University of Nottingham and the MRC inform the press of successful research.

Helicobacter pylori (Hp) colonizes the stomachs of approximately half the world?s population and is associated with peptic ulceration and gastric malignancy. Hp usually establishes an asymptomatic infection, and provokes a vigorous but ineffective immune response which permits life-long persistence in the gastric mucosa. This implies that inflammation is modulated, and the mechanisms of immune subversion remain unclear.
It was previously reported that Hp-induced pathology is determined by the acquired immune response to infection. In recent observational studies, we have shown for the first time that certain human Treg responses are associated with protection from Hp-mediated peptic ulcer disease. We therefore hypothesise that Hp expresses factors which drive Treg responses, resulting in the evasion of immunity and promoting persistence in the gastric mucosa.
For this project, we wish to characterise the regulatory T-cells in the blood and gastric mucosa of H. pylori-infected donors and investigate their antigenic specificity. We will carry out interventional experiments in mice to determine if disease severity is indeed determined by the level of the Treg response, and examine the effects of regulatory T-cell-inducing bacterial factors in vivo. These studies will allow us to discover whether differences between strains influence the response elicited, and if this might explain differences in disease severity and persistence of the infection. Understanding the factors that allow the bacteria to persist in the stomach may lead to future advances in the development of effective vaccines.