IMPORTANCE OF CYTOTOXIC T-LYMPHOCYTES IN THE REJECTION OF TRANSPLANTED HEPATOCELLULAR-CARCINOMA

Fischer rats became resistant to syngeneic hepatocellular carcinoma (F AA-HTC1) cells on repeated sensitization with mitomycin C-treated FAA- HTC1 cells. In contrast, FAA-HTC1 cells injected into the liver killed normal control Fischer rats within 2 months. Histopathological studie s revealed massive accumulation of mononuclear cells in the tumor tiss ues of sensitized rats that rejected syngeneic FAA-HTC1 cells, whereas very few mononuclear cells were found in the tumor tissues of control rats. Cell populations infiltrating the tumor tissues were identified by flow cytometric analysis. Mononuclear cells found within the regre ssing tumors of the sensitized rats were identified as mostly T cells, and two-thirds of these T cells were CD8-positive. Compared with the activity in control rats, the killer activity of mononuclear cells inf iltrating tumors was significantly increased in the sensitized rats 7 days after tumor inoculation. Depletion of CD8(+) T cells significantl y reduced the cytotoxicity of mononuclear cells infiltrating tumors ob tained from sensitized rats. In contrast, depletion of CD16(+) cells r educed the cytotoxicity of mononuclear cells infiltrating tumors obtai ned from both control and sensitized rats. Furthermore, the CD16(+) ce ll-depleted fraction of mononuclear cells infiltrating tumors showed s ignificant cytotoxicity against FAA-HTC1 cells, but failed to show cyt otoxicity against other syngeneic tumor cells or allogeneic hepatoma c ells.