Kinetics of the transfer of tumor-specific cytotoxicity with immune RNA

Abstract

The optimal conditions for the transfer of cell-mediated cytotoxicity (CMC) with xenogenic immune RNA (I-RNA) were studied. Unsensitized mouse lymphocytes were converted to effector cells specifically cytolytic to syngeneic tumor cells by incubation of these lymphocytes with I-RNA extracted from the lymphoid tissues of guinea pigs immunized with the murine tumor being tested. I-RNA was RNase sensitive but DNase and pronase resistant. Lymphoid RNA extracted from guinea pigs that had been injected with complete Freund's adjuvant without tumor was ineffective. The most effective I-RNA was harvested from guinea pigs 14 days after immunization with murine tumor. Maximum cytolytic activity was observed with mouse lymphocytes that had been incubated with I-RNA at a concentration of 500 μg/ml at 37°C for 30 min. Significant tumor cell destruction did not occur until 48 hr after the addition of RNA-incubated lymphocytes to target cells. Significant CMC was seen at a broad range of lymphocyte to target cell ratios (100:1–1000:1). Lymphoid cells obtained from spleen, bone marrow, thymus, and lymph nodes of normal mice could be converted by I-RNA to become effector killer cells. The treatment of lymphocytes with anti-θ serum and complement prior to incubation with I-RNA abolished the CMC transferred by I-RNA.