Induction of nonspecific killer T cells from non-immune mouse spleen cells by culture with interleukin 2.
Culture fluids of concanavalin A-stimulated rat spleen cells were purified by means of ammonium sulfate precipitation and Sephacryl S-200 column chromatography. Interleukin 2 (IL-2), which can promote the proliferation of mouse lymphocytes was distributed in the fractions of molecular weight of 22,000 to 26,000 daltons. Culture of C57BL/6 mouse spleen cells with the IL-2 fraction resulted in the induction of cells cytotoxic to syngeneic fibrosarcoma cells. Determination of the target specificity of the killer cells revealed that the killer cells could lyse a variety of syngeneic and allogeneic tumor cells in vitro. The results of cold target inhibition tests and cytotoxicity assay after treatment with antisera plus complement indicated that the killer cells mainly consisted of Thy 1.2+, Ly 2.2+, asialoGM1-T cells but included some asialo-GM1+ natural killer (NK) cells. Although the cytotoxicities of both IL-2-activated killer T cells and NK cells were nonspecific in terms of the antigen specificity, their cytotoxic activities against syngeneic fibrosarcomas and NK-sensitive allogeneic lymphomas were complementary. The assay of interferon in culture fluid from IL-2-treated spleen cells suggested that generation of IL-2-activated killer cells was closely associated with the amount of immune interferon released from lymphocytes in the culture.