CELL-MEDIATED IMMUNE RESPONSE OF IN VITRO SENSITIZED LYMPHOCYTES TO ISOGENEIC METHYL-CHOLANTHRENE-INDUCED TUMOR CELL LINES

Abstract

Lymphocytes were immunized to tumor cells in vitro and the lymphocyte-mediated destruction of target cells as well as the production of migration inhibition factor were studied. As target cells, several isogeneic methylcholanthrene-induced tumor cell (MCA-TC) lines from C57BL mice were used. A primary immune response to MCA-TC was produced in a modified Mishell-Dutton system. Spleen cells from C57BL mice were cultured for 4 days in the presence or absence of the phytomitogens phytohemagglutinin and concanavalin A. The in vitro induced immune response to MCA-TC was detected by the microcytotoxicity test described by Takasugi and Klein and by a macrophage migration inhibition test. The results indicate that in vitro immunized lymphocytes are cytotoxic to MCA-TC; the reaction is specific for the target cell line which was used as immunizing agent in vitro. In the presence of antigenic material, migration inhibition factor is released from the in vitro immunized lymphocytes. The in vitro induced immune response is significantly enhanced by the phytomitogens phytohemagglutinin and concanavalin A. The cytotoxic reaction is target cell-specific when the phytomitogens were used in submitogenic doses. Using different isogeneic MCA-TC lines as inducer cells and target cells, the most effective cytotoxic reaction was observed with the tumor cell line to which the lymphocytes were immunized. Only in some experiments was a cross reactivity between the isogeneic tumor cell lines demonstrated. The results suggest that common antigens are detected by in vitro immunized lymphocytes, but the immune response to these antigens seems to be weak as compared to that induced by the individual antigens of each tumor cell line.