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International Immunology, Vol. 16, No. 2, pp. 215-222, February 2004
© 2004 Japanese Society for Immunology

Impaired IFN-{gamma} production of V{alpha}24 NKT cells in non-remitting sarcoidosis

Seiichiro Kobayashi1, Yoshikatsu Kaneko1, Ken-ichiro Seino4,5, Yoshihito Yamada2, Shinichiro Motohashi1, Junzo Koike1, Kaoru Sugaya1, Takayuki Kuriyama2, Shigetaka Asano6, Tomiyasu Tsuda7, Hiroshi Wakao4, Michishige Harada4, Satoshi Kojo4, Toshinori Nakayama1,3 and Masaru Taniguchi1,4

Departments of 1 Molecular Immunology, 2 Respirology and 3 Medical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 4 Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan 5 PRESTO, Japan Science and Technology Corp., Saitama 332-0012, Japan 6 Division of Molecular Therapy, Institute of Medical Science, University of Tokyo, Tokyo 113-0033, Japan 7 Third Department of Internal Medicine, Oita Medical University, Oita 879-5593, Japan

The first two authors contributed equally to this work
Correspondence to: M. Taniguchi; E-mail: taniguti{at}med.m.chiba-u.ac.jp
Transmitting editor: M. Miyasaka

Sarcoidosis is a systemic disorder associated with granuloma characterized by an abnormal Th1-type cytokine production and accumulation of Th1 CD4 T cells in the granuloma lesions, suggesting an importance of Th1 responses in sarcoidosis. However, the pathogenesis of sarcoidosis remains to be solved. Here, we investigated the nature of V{alpha}24 NKT cells with immunoregulatory functions in sarcoidosis. Patients with non-remitting sarcoidosis displayed a decrease in the number of V{alpha}24 NKT cells in peripheral blood, but an accumulation of these cells in granulomatous lesions. When stimulated with the specific glycolipid ligand, {alpha}-galactosylceramide, peripheral blood V{alpha}24 NKT cells from patients with non-remitting disease produced significantly less IFN-{gamma} than those from healthy volunteers, but normal levels of IL-4. The reduced IFN-{gamma} production was observed only in V{alpha}24 NKT cells and not conventional CD4 T cells, but was normal in patients with remitting disease, suggesting that non-remitting sarcoidosis involves an insufficient IFN-{gamma} production of V{alpha}24 NKT cells which is well correlated with disease activity. Thus, these results suggest that V{alpha}24 NKT cells play a crucial role in the disease status of sarcoidosis.

Keywords: cytokine, human, inflammation, lung, Th1/Th2 cell


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