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NK cells and Regulatory T cells in Helicobacter pylori infection

Group leader: Samuel Lundin (Associate professor/Docent, Ph.D.)
Members: Jenni Adamsson (Research technician), Bert Kindlund (Ph.D. student), Åsa Lindgren (Ph.D. student).

Helicobacter pylori cause a life-long infection of the human stomach. While the majority of the infected subjects remain asymptomatic, subsets of individuals develop duodenal ulcers or gastric adenocarcinoma as a result of their infection. The main aim of this project is to investigate the role of regulatory T cells (Treg) and NK cells in the immune response to H. pylori infection, and wether these cells are involved in the development of adenocarcinoma or ulcer disease or in the protection against disease development in asymptomatic individuals. We also aim to develop strategies to identify patients at risk of developing disease, based on characteristics of their immune response to H. pylori.

Our previous studies have shown that Treg are present in increased numbers in the infected compared to uninfected gastric mucosa, and that these cells suppress the T-cell response to H. pylori. Furthermore, even higher numbers of Treg are found in the tumour areas of patients suffering from gastric adenocarcinoma. We now aim to study the mechanisms used by these gastric Treg in order to find ways to interfere with disease development in H. pylori-infected individuals.

We have further showed that NK cells do become activated to produce IFN-γ when stimulated by H. pylori components, and that both gastric and systemic NK cells from gastric cancer patients are refractory to stimulation. In our current studies we are elucidating the mechanisms for NK-cell activation by H. pylori, mainly by studying the involvement of different toll-like receptors. Furthermore we also investigate reasons for the suppressed NK-cell response observed in gastric cancer patients.

Important publications:
Yun CH, Lundgren A, Azem J, Sjöling Å, Holmgren J, Svennerholm A-M and Lundin BS. (2005) Natural killer cells and Helicobacter pylori-infection: bacterial antigens and interleukin-12 act synergistically to induce interferon-gamma production. Infect Immun. 73:1482-90.

Lundgren A, Strömberg E, Sjöling Å, Lindholm C, Enarsson K, Edebo A, Johnsson E, Suri-Payer E, Svennerholm A-M and Lundin BS. (2005) Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients. Infect Immun. 73:523-31.

Enarsson K, Lundgren A, Kindlund B, Hermansson M, Roncador G, Banham AH, Lundin BS and Quiding-Järbrink M. (2006) Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma. Clin Immunol. In press.

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2007-03-26

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