To determine the role of NK cells in regulation of tissue growth, the
phenotype and Function of liver-resident NK cells were studied after 7
0% partial hepatectomy in rats. The process of liver regeneration was
generally completed by day 14. In contrast, the number of liver-reside
nt NK cells (NKR-P1(bright)) was restored as early as day 3 after part
ial hepatectomy. However, spontaneous functions of liver-resident NK c
ells, including killing of YAC-1 and P815 targets, Ab-dependent eel lu
lar cytotoxicity, and redirected killing via NKR-P1, were continuousl
y suppressed throughout the entire period of liver regeneration (from
3 h to 14 days). Augmentation of NK cytotoxicity against P815 targets
and induction of NK cell adherence to plastic following 24 h of IL-2 s
timulation showed a similar pattern of suppression. However, IL-2-indu
ced augmentation of YAC-1 killing, proliferation and generation of adh
erent NK cells, and LAK activity in 5- to 7-day cultures were found to
he suppressed only during the first 24 h and increased between days 2
and 7 after hepatectomy. Sorted NK cells (greater than or equal to 95
% NKR-P1(bright)) from liver-resident mononuclear leukocytes 24 h afte
r partial hepatectomy showed the same pattern of suppression as unsort
ed mononuclear leukocytes. In contrast to liver-resident NK cells, no
significant changes were detected in peripheral blood or spleen NK cel
ls of rats following partial hepatectomy. Of particular interest, in n
ormal liver, hepatocytes were resistant to NK lysis, while resident NK
cells were cytotoxic for various NK-sensitive targets. In contrast, d
uring the early period of liver regeneration, when hepatocytes were se
nsitive to lysis by liver-resident NK cells of normal rats, NK cells o
btained from regenerating liver tissues were unable to mediate cytotox
icity. At the final phase of liver regeneration (days 7-14 after hepat
ectomy), both resistance of hepatocytes to killing by NK cells and cyt
otoxicity of liver-resident lymphocytes against hepatocytes from regen
erating liver were simultaneously restored. In vivo depletion of NK ce
lls by injection of rats with anti-NKR-P1 mAb resulted in a significan
t augmentation of liver regeneration subsequent to partial hepatectomy
. Our data suggest that liver-resident NK cells may be involved in reg
ulation of the extent of liver regeneration.