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Relationship between lymphocyte proliferation and tumor-specific cytotoxicity after immune RNA treatment.

Normal mouse lymphocytes were converted to effector cells cytolytic to syngeneic mouse tumor cells in vitro by incubating these lymphocytes with immune RNA (I-RNA) extracted from the lymphoid tissues of guinea pigs immunized with the same mouse tumor. This effect was tumor specific, RNase sensitive, and DNase and pronase resistant. These I-RNA-incubated lymphocytes were also able to undergo proliferation when they were co-cultured with specific tumor cells in tissue culture. Treatment with mitomycin C completely inhibited the blast transformation of I-RNA-incubated lymphocytes in response to specific tumor antigen, whereas the cytotoxic activity of mitomycin C-treated lymphocytes was not affected. There was no significant alteration in cytotoxic capability when lymphocytes were cultured for 0, 24, 48, or 72 hr after I-RNA incubation before testing. The time necessary for I-RNA-incubated lymphocytes to kill specific target cells was not different whether the lymphocytes had been cultured for 48 hr or tested immediately after I-RNA treatment. These results suggest that a proliferative step is not necessary after I-RNA treatment for lymphocytes to manifest tumor-specific cytotoxicity and that I-RNA may act upon at least two different sets of lymphocytes; one undergoing cellular proliferation in response to specific tumor antigen and the other manifesting tumor-specific cellular cytotoxicity.