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International Immunology Advance Access originally published online on October 11, 2004
International Immunology 2004 16(12):1733-1739; doi:10.1093/intimm/dxh174
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© 2004 The Japanese Society for Immunology

IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8

Hitomi Hata1, Tomohiro Yoshimoto2,3, Nobuki Hayashi2,3, Toshikazu Hada1 and Kenji Nakanishi2,3

1 Department of Internal Medicine and 2 Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
3 Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan

Correspondence to: K. Nakanishi; E-mail: nakaken{at}hyo-med.ac.jp

Although IL-18 was initially regarded as a factor that enhances IFN-{gamma} production from Th1 cells, later studies revealed its potential to induce Th2 cytokine production from T cells, NK cells and basophils/mast cells. Very recently, we demonstrated that passively transferred memory phenotype Th1 cells induce airway inflammation and hyperresponsiveness in a host mouse by production of Th1-, Th2-cytokines, GM-CSF and chemokines, when the transferred cells are stimulated in the host mice with nasally administered Ag and IL-18. Moreover, IL-18 is suggested to contribute to asthma exacerbation in human patients. Therefore, it is important to determine whether human Th1 cells also have the potential to produce these soluble factors when stimulated with anti-CD3 and IL-18 in vitro. Here we demonstrated that only Th1 cells, but not Th2 cells, produce IFN-{gamma}, IL-13, GM-CSF and IL-8 after stimulation with anti-CD3 and IL-18. Furthermore, highly purified IFN-{gamma}-producing Th1 cells have the same potential. Thus, human Th1 cells may become very harmful cells, when stimulated with Ag and IL-18 in vivo, and produce IFN-{gamma}, IL-13, GM-CSF and IL-8, which in combination might induce severe inflammation such as airway inflammation.

Keywords: allergy, IFN-{gamma}, IL-13, IL-8, human Th1 cells

Transmitting editor: T. Hamaoka


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