Cytotoxic NK1.1 Ag⁺ αβ T cells with intermediate TCR induced in the liver of mice by IL-12

Systemic administration of IL-12 greatly reduced the hepatic metastases 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 cytotoxicity was observed in splenocytes in normal and nude mice. After IL-12 administration, hepatic MNC increased in number and showed vigorous proliferation in vitro. Hepatic MNC of control C57BL/6 +/+ mice contain αβ T cells with intermediate TCR (TCR(int)) as well as αβ 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⁺ (NK1⁺ TCR(int)). Systemic administration of IL-12 into normal and nude mice markedly augments the NK1 expression of NK1⁺ TCR(int) cells (NK1(high) TCR(int)), which is comparable to or brighter than that of NK cells in the liver, whereas αβ T cells with bright TCR or γδ 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-treated normal mice by respective Abs and C in vitro abrogate their cytotoxicity. These results revealed that TCR(int) cells are potent cytotoxic effector cells and suggest that NK1(high) TCR(int) cells are the main antimetastatic population in the liver, and that TCR(int) cells are functionally different from regular T cell is with bright TCR.