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J Med Microbiol 53 (2004), 21-29; DOI: 10.1099/jmm.0.05348-0
© 2004 Society for General Microbiology
ISSN 0022-2615

Immune response in Helicobacter pylori-induced low-grade gastric-mucosa-associated lymphoid tissue (MALT) lymphoma

Rie Yamasaki1, Kenji Yokota2, Hiroyuki Okada3, Shyunji Hayashi4, Motowo Mizuno3, Tadashi Yoshino1, Yoshikazu Hirai4, Daizou Saitou5, Tadaatsu Akagi1 and Keiji Oguma2

1,2,3Departments of Pathology1, Bacteriology2 and Medicine and Medical Science3, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan 4Department of Infection and Immunity, Jichi Medical School, 3311-1 Yakushiji, Minami-kawauchi, Tochigi 326-0498, Japan 5National Cancer Center, Central Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan

Correspondence Kenji Yokota yokochan{at}md.okayama-u.ac.jp

Received June 10, 2003
Accepted October 21, 2003

We have reported previously that heat-shock protein 60 kDa (hsp60) of Helicobacter pylori is an important antigen in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In order to investigate associations with host immune reactions and hsp60 antigen, CD40 ligand (CD40L) expression and cytokine production were analysed following stimulation with hsp60. To provide a clear antigen-driven immune response, peripheral blood mononuclear cells (PBMC) from patients with low-grade MALT lymphoma and gastritis and those from healthy volunteers were stimulated with recombinant H. pylori hsp60 and H. pylori cell lysate in the presence of cytokines (IL4 and granulocyte-macrophage colony-stimulating factor). mRNA expression was also analysed by a cDNA microarray containing 1100 genes. Expression of CD40L on PBMCs of patients with MALT lymphoma was increased by cytokines or by combination with stimulation with hsp60 antigens. The production of IL4 in PBMC cultures was increased in patients with MALT lymphoma; however, production of IFN-{gamma} was at low levels. DNA microarray analysis indicated increased levels of HLA-DR and integrin mRNAs. In cases of low-grade MALT lymphoma, adaptive immune responses against hsp60 may be enhanced by host factors, such as antigen presentation and T-cell activation, resulting in B-cell proliferation, which can be demonstrated during chronic H. pylori infection.

Abbreviations: APC, antigen-presenting cell; DC, dendritic cell; FDC, follicular dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; hsp, heat-shock protein; MALT, mucosa-associated lymphoid tissue; PBMC, peripheral blood mononuclear cell; Th, T helper.




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