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NK cells as living body regulation-especially on the roles of hepatic NK cells

NK细胞作为活体调节——尤其是肝脏NK细胞的作用

基本信息

批准号：
63570218
负责人：
ABO Toru
金额：
$ 1.34万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

NK cells originally received an attention because of their antitumor function. Thereafter, as it was demonstrated that NK cells could mediate their cytotoxic function against rapid dividing normal cells, they were considered to have another function as living body regulation. Surrounding by this situation, we decided to investigate on the present project. Especially at that time, we identified NK cells in the liver. We therefore purposed to characterize their nature and reveal their physiological functions. The evidences during these two years are summarized as follows.1) In the liver of mice, the proper lymphocytes existed and approximately 25% of such lymphocytes were NK cells. This level was higher than those of any other immune organs. 2) The level of hepatic NK cells were variable, showing a unique age-dependency. The level of hepatic NK cells got a peak at the age of 6 weeks, when intensive increases of their body weight and hepatic weight were stopped, and then decreased. 3) The … More hepatic NK cells did not mediate their cytotoxicity against the hepatocytes in a resting state but mediated the cytotoxicity against regenerating hepatocytes.The above experimental results, 1) to 3), indicate that NK cells in the liver may function as a regulatory system for the hepatocyte regeneration which occurs physiologically and at emergency.4) It was revealed that NK susceptibility of target cells was increased when the expression of classI MHC antigens on NK target cells was decreased. We also developed a new method that classI MHC antigens on the living cells were eliminated by acid-treatment at pH3.0. We confirmed the above phenomenon by using this methods and revealed in part the underlying mechanisms. 5) The regenerating hepatocytes in vivo and the in vitro dividing hepatocytes in the presence of EGF showed apparently the decreased expression of classI MHC antigens on their surface and the NK susceptibility correlated well to such changes. 6) Developing from NK cell study in the liver, we demonstrated for the first time a number of gamma delta T lymphocytes existed in the mononuclear cells of the liver. Less

NK细胞最初因其抗肿瘤功能而受到关注。此后，由于证明NK细胞可以介导其针对快速分裂的正常细胞的细胞毒性功能，因此认为它们具有作为活体调节的另一功能。在这种情况下，我们决定对本项目进行调查。特别是在那个时候，我们在肝脏中发现了NK细胞。因此，我们的目的是描述他们的性质，揭示他们的生理功能。这两年的研究结果表明：1）小鼠肝脏中存在正常的淋巴细胞，其中约25%为NK细胞;这个水平比任何免疫器官都要高。2)肝脏NK细胞的水平是可变的，显示出独特的年龄依赖性。肝脏NK细胞水平在6周龄时达到高峰，此时体重和肝脏重量的急剧增加停止，随后下降。3)的 ...更多信息肝NK细胞在静止状态下不介导它们对肝细胞的细胞毒性，但介导对再生肝细胞的细胞毒性。上述实验结果，1）至3），表明肝脏中的NK细胞可能作为生理上和紧急情况下发生的肝细胞再生的调节系统。4）结果表明，当NK细胞表面MHC Ⅰ类抗原表达降低时，NK细胞的NK敏感性增加。我们还开发了一种新的方法，通过pH3.0的酸处理消除活细胞上的I类MHC抗原。我们用这种方法证实了上述现象，并揭示了部分潜在的机制。5)在体内再生的肝细胞和在体外分裂的肝细胞中，EGF的存在下，其表面的I类MHC抗原的表达明显减少，NK敏感性与这种变化密切相关。6)通过对肝脏NK细胞的研究，我们首次证实了肝脏单核细胞中存在大量γ δ T淋巴细胞。少