トキタ ダイスケ
TOKITA Daisuke
時田 大輔 所属 医学部 医学科(東京女子医科大学病院) 職種 非常勤講師 |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice. |
掲載誌名 | 正式名:Hepatology (Baltimore, Md.) 略 称:Hepatology ISSNコード:02709139/02709139 |
掲載区分 | 国外 |
巻・号・頁 | 39(5),pp.1321-31 |
著者・共著者 | Ochi Makoto, Ohdan Hideki, Mitsuta Hiroshi, Onoe Takashi, Tokita Daisuke, Hara Hidetaka, Ishiyama Kohei, Zhou Wendy, Tanaka Yuka, Asahara Toshimasa |
発行年月 | 2004/05 |
概要 | Although it is known that activation of natural killer (NK) cells causes liver injury, the mechanisms underlying NK cell-induced killing of self-hepatocytes are not clear. We demonstrated that liver NK cells have cytotoxicity against normal syngeneic hepatocytes in mice. Polyinosinic-polycytidylic acid (poly I:C) treatment enhanced hepatocyte toxicity of liver NK cells but not that of spleen NK cells. Unlike NK cells in other tissues, approximately 30%-40% of liver NK cells constitutively express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). An in vitro NK cell cytotoxic assay revealed that hepatocyte toxicity of liver NK cells from both naïve and poly I:C-treated mice was inhibited partially by an anti-TRAIL monoclonal antibody (mAb) alone and completely by the combination with anti-Fas ligand (FasL) mAb and a perforin inhibitor, concanamycin A, indicating contribution of TRAIL to NK cell-mediated hepatocyte toxicity. The majority of TRAIL(+) NK cells lacked expression of Ly-49 inhibitory receptors recognizing self-major histocompatibility complex class I, indicating a propensity to targeting self-hepatocytes. Poly I:C treatment significantly upregulated the expression of Ly-49 receptors on TRAIL(-) NK cells. This might be a compensatory mechanism to protect self-class I-expressing cells from activated NK cell-mediated killing. However, such compensatory alteration was not seen at all in the TRAIL(+) NK cell fraction. Thus, liver TRAIL(+) NK cells have less capacity for self-recognition, and this might be involved in NK cell-dependent self-hepatocyte toxicity. In conclusion, our findings are consistent with a model in which TRAIL-expressing NK cells play a critical role in self-hepatocyte killing through poor recognition of MHC. |
DOI | 10.1002/hep.20204 |
PMID | 15122761 |