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

NK细胞最初因为其抗肿瘤功能而受到关注。此后，由于NK细胞可以介导其对快速分裂的正常细胞的细胞毒作用，因此它们被认为具有另一种活体调节功能。在这种情况下，我们决定对目前的项目进行调查。特别是当时，我们在肝脏中发现了NK细胞。因此，我们打算刻画它们的性质，并揭示它们的生理功能。1)在小鼠肝脏中存在正常淋巴细胞，其中约25%为NK细胞。这一水平高于任何其他免疫器官。2)肝NK细胞水平变化较大，具有独特的年龄依赖性。肝脏NK细胞水平在6周龄时达到高峰，体重和肝脏重量的剧烈增长停止后下降。3)The…以上实验结果(1)~3)表明，肝脏中的NK细胞可能作为生理性和应急性肝细胞再生的调节系统。4)当NK靶细胞表面Classi MHC抗原的表达减少时，靶细胞的NK敏感性增加。我们还开发了一种新的方法，即用pH 3.0的酸处理来消除活细胞上的Classi MHC抗原。我们用这种方法证实了上述现象，并部分揭示了其潜在的机制。5)体内再生肝细胞和体外分裂肝细胞在EGF存在下，其表面Classi MHC抗原的表达明显减少，NK细胞的敏感性与此变化密切相关。6)在肝脏NK细胞研究的基础上，首次发现肝脏单个核细胞中存在大量的γ-Delta T淋巴细胞。较少

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