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Infection and Immunity, March 2005, p. 1482-1490, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1482-1490.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Natural Killer Cells and Helicobacter pylori Infection: Bacterial Antigens and Interleukin-12 Act Synergistically To Induce Gamma Interferon Production

Cheol H. Yun,1,2 Anna Lundgren,1 Josef Azem,1 Åsa Sjöling,1 Jan Holmgren,1 Ann-Mari Svennerholm,1 and B. Samuel Lundin1*

Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX), Göteborg University, Göteborg, Sweden,1 International Vaccine Institute, Kwanak-gu, Seoul, Korea2

Received 18 July 2004/ Returned for modification 25 August 2004/ Accepted 8 November 2004

Helicobacter pylori is known to induce a local immune response, which is characterized by activation of lymphocytes and the production of IFN-{gamma} in the stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are potent producers of gamma interferon (IFN-{gamma}), we investigated whether NK cells play a role in the immune response to H. pylori infection. Our results showed that NK cells were present in both the gastric and duodenal mucosae but that H. pylori infection did not affect the infiltration of NK cells into the gastrointestinal area. Furthermore, we could show that NK cells could be activated directly by H. pylori antigens, as H. pylori bacteria, as well as lysate from H. pylori, induced the secretion of IFN-{gamma} by NK cells. NK cells were also activated without direct contact when separated from the bacteria by an epithelial cell layer, indicating that the activation of NK cells by H. pylori can also occur in vivo, in the infected stomach mucosa. Moreover, the production of IFN-{gamma} by NK cells was greatly enhanced when a small amount of interleukin-12 (IL-12) was added, and this synergistic effect was associated with increased expression of the IL-12 receptor ß2. It was further evident that bacterial lysate alone was sufficient to induce the activation of cytotoxicity-related molecules. In conclusion, we demonstrated that NK cells are present in the gastroduodenal mucosa of humans and that NK cells produce high levels of IFN-{gamma} when stimulated with a combination of H. pylori antigen and IL-12. We propose that NK cells play an active role in the local immune response to H. pylori infection.

* Corresponding author. Mailing address: Department of Medical Microbiology and Immunology and Göteborg University Vaccine Institute (GUVAX), Göteborg University, Box 435, 40530 Göteborg, Sweden. Phone: 46 317 736207. Fax: 46 317 736205. E-mail: samuel.lundin{at}microbio.gu.se.

Editor: A. D. O'Brien

Infection and Immunity, March 2005, p. 1482-1490, Vol. 73, No. 3
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.3.1482-1490.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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