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

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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