CYTOTOXIC NK1.1 AG-BETA T-CELLS WITH INTERMEDIATE TCR INDUCED IN THE LIVER OF MICE BY IL-12( ALPHA)

Systemic administration of IL-12 greatly reduced the hepatic metastase s of i.v.-injected liver metastatic EL4 tumor cells in C57BL/6 +/+ and nu/nu mice. Cytotoxic assay in vitro revealed that administration of IL-12 greatly enhanced cytotoxicity of hepatic mononuclear cells (MNC) against various NK- sensitive and -resistant tumor targets, including EL4 cells, whereas only slight or moderate augmentation of the cytoto xicity was observed in splenocytes in normal and nude mice. After IL-1 2 administration, hepatic MNC increased in number and showed vigorous proliferation in vitro. Hepatic MNC of control C57BL/6 +/+ mice contai n alpha beta T cells with intermediate TCR (TCR(int)) as well as alpha beta T cells with bright TCR, whereas hepatic MNC of nu/nu mice have only TCR(int) cells. These TCR(int) cells are found to be NK1.1 Ag+ (N K1(+) TCR(int)). Systemic administration of IL-12 into normal and nude mice markedly augments the NK1 expression of NK1(+) TCR(int) cells (N K1(high) TCR(int)), which is comparable to or brighter than that of NK cells in the liver, whereas alpha beta T cells with bright TCR or gam ma delta T cells in the liver are NK1(-). Depletion of either NK1.1(+) or CD3(+) cells, but not CD8(+) cells, of hepatic MNC from IL-12-trea ted normal mice by respective Abs and C in vitro abrogate their cytoto xicity. These results revealed that TCR(int) cells are potent cytotoxi c effector cells and suggest that NK1(high) TCR(int) cells are the mai n antimetastatic population in the liver, and that TCR(int) cells are functionally different from regular T cells with bright TCR.