免疫細胞機能解明の生理学的アプローチ : ヒトナチュラルキラー細胞の標的細胞傷害機構の解析(免疫学の進歩-基礎と臨床-,シンポジウム,東京女子医科大学学会第308回例会)

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Despite of striking advance in immunological researches, the process occurring in stimulating or stimulated cells has scaresly been investigated by physiological methods, and, in many cases, little is known about whether and how novel cellular molecules found by virtue of molecular biology operate in the physiological condition. Here we introduce our recent work on the cytotoxicity of human natural killer (NK) cells, based on continuous imaging of intracellular Ca^<2+> and morphologic changes of individual NK cells and target cells. This method enabled us to examine the time cource and aspects of cell-to-cell interaction and to identify the mode of cell death of target cells, either necrosis due to membrane damage or apoptosis due to nuclear damage. Ca^<2+> imaging demonstrated that NK cells are activated within 2 min after contact with target cellls, and that activated NK cells induces necrosis in target cell lines within several min by permeabilizing the cells through pores formed by perforin which is released from NK cells. Morphologic observation of the cell and nucleus showed that NK cells induce apoptosis in the majority of target cells of cell lines expressing high levels of Fas receptors, the apoptosis-inducing surface antigen. Fas ligand (FasL) was found to be expressed in freshly isolated NK cells, using RT-PCR. The function of FasL/Fas interaction was elucidated by the following findings. 1) NK cell-induced apoptosis was observed in Ca^<2+>-free medium in which perforin pore is known not to be formed. 2) Apoptosis in Ca^<2+>-free medium was inhibited by an anti-Fas monoclonal antibody in a dose-dependent manner. 3) Transfection of the Fas gene in target cells facilitated the induction of apoptosis, compared with the parental cell line. We emphasize that physiological aproaches should be more applied to elucidate the functional mechanism of immune cells.
東京女子医科大学の論文
1997-06-25

免疫細胞機能解明の生理学的アプローチ : ヒトナチュラルキラー細胞の標的細胞傷害機構の解析(免疫学の進歩-基礎と臨床-,シンポジウム,東京女子医科大学学会第308回例会)

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