The Journal of Immunology, Vol 141, Issue 1 315-323, Copyright © 1988 by American Association of Immunologists

ARTICLES

Age-related variation in the proportion and activity of murine liver natural killer cells and their cytotoxicity against regenerating hepatocytes

H Itoh, T Abo, S Sugawara, A Kanno and K Kumagai
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.

We investigated the distribution of liver NK cells in mice of various ages and their cytotoxicity against regenerating hepatocytes. Liver NK cells were identified by asialo GM1 antibody in mononuclear cell suspension from the liver, whereas NK activity was assayed against YAC- 1 target cells. Mononuclear cells in the liver consisted of more than 25% NK cells with potent NK activity in C3H/He mice, 8 wk of age. The strain-specific distribution (C3H/He greater than C57BL/6 greater than DBA/2) of liver NK cells was the same as those in the spleen and blood. The proportion of liver NK cells and the level of NK activity in C3H/He mice were further demonstrated to vary depending on age, in that both the proportion and the function were generated at 4 wk of age, reached a maximum between the 6th and 8th wk, and then rapidly decreased around the 9th wk. The appearance of an increased number of NK cells in the liver seemed to coincide with the slowing of the rapid increase of murine liver weight. We then investigated whether liver NK cells mediated their cytotoxicity against regenerating hepatocytes. Both specific 51Cr-release assay and single cell cytotoxicity assay demonstrated that liver NK cells were significantly cytotoxic against regenerating hepatocytes in partially hepatectomized liver, but to a lesser extent against normal hepatocytes in resting liver. Morphologic study revealed that normal liver predominantly consisted of hepatocytes with binuclei (greater than 60%) but that regenerating liver mainly consisted of hepatocytes with a single nucleus (greater than 70%). One- nucleus hepatocytes were more susceptible to the cytotoxicity of liver NK cells. A comparative study of restoration kinetics of the liver weight and the number of liver NK cells after partial hepatectomy also showed a unique relationship. These results raise the possibility that liver NK cells might be responsible for regulating hepatocyte growth.

This article has been cited by other articles:

				S. Ogawa, Y.-i. Tagawa, A. Kamiyoshi, A. Suzuki, J. Nakayama, Y. Hashikura, and S. Miyagawa Crucial Roles of Mesodermal Cell Lineages in a Murine Embryonic Stem Cell-Derived In Vitro Liver Organogenesis System Stem Cells, August 1, 2005; 23(7): 903 - 913. [Abstract] [Full Text] [PDF]

				S. Suzuki, S. Fujieda, H. Sunaga, C. Yamamoto, H. Kimura, and F. Gejyo Synthesis of immunoglobulins against Haemophilus parainfluenzae by tonsillar lymphocytes from patients with IgA nephropathy Nephrol. Dial. Transplant., May 1, 2000; 15(5): 619 - 624. [Abstract] [Full Text] [PDF]

				T. Matsushita, K. Ando, K. Kimura, H. Ohnishi, M. Imawari, Y. Muto, and H. Moriwaki IL-12 induces specific cytotoxicity against regenerating hepatocytes in vivo Int. Immunol., May 1, 1999; 11(5): 657 - 665. [Abstract] [Full Text] [PDF]

				S. G. Shaw, A. A. Maung, R. J. Steptoe, A. W. Thomson, and N. L. Vujanovic3 Expansion of Functional NK Cells in Multiple Tissue Compartments of Mice Treated with Flt3-Ligand: Implications for Anti-Cancer and Anti-Viral Therapy J. Immunol., September 15, 1998; 161(6): 2817 - 2824. [Abstract] [Full Text] [PDF]