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Relationship between Lymphocyte Proliferation and Tumor-Specific Cytotoxicity after Immune RNA Treatment¹

Departments of Pathology and Surgery, Harvard Medical School, Peter Bent Brigham Hospital, Boston, Massachusetts 02115

Abstract

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.

Footnotes

¹ This work was supported by United States Public Health Service Grant CA 21644 and a Biomedical Research Support Grant 5S07RR05489-16.