In vitro lymphocyte stimulation and the generation of cytotoxic lymphocytes with drug-induced antigenic lymphomas.

New antigenic specificities, not detectable on parental cells and transmissible after the withdrawal of the drug treatment, have been induced in mouse lymphomas. Studies were conducted of proliferative stimulation of syngeneic lymphocytes and the generation of cytotoxic lymphocytes (CL's) in a mixed lymphocyte-tumor cell culture system by 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC)-induced antigens in L1210 and EL4 leukemia sublines. The DTIC-induced antigens were observed to stimulate [3H]thymidine uptake by normal and primed syngeneic lymphocytes and to generate specific CL's to DTIC-altered cells. The specificity of the in vitro immune reactivity was demonstrated. Characteristics of lymphocyte triggering, including the optimal ratio of stimulating cells to responding cells, the kinetics of CL activation, and the quantitation of CL activity, were also evaluated. DTIC antigens on leukemic cells can activate syngeneic lymphocytes and can act as target antigens in cell-mediated immunity. The experimental data support the transplantation antigen-like nature of DTIC-induced antigens.