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Relationship of Cellular Proliferation and the Generation of Cytotoxic Cells in an in Vitro Secondary Immune Response to Syngeneic Rat Lymphoma Cells¹

Division of Tumor Immunology, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, Washington 98104; and Departments of Pediatrics, Medicine, and Microbiology, University of Washington School of Medicine, Seattle, Washington 98195

Abstract

The role of cellular proliferation for the generation of cytotoxic activity in an in vitro secondary immune response to syngeneic lymphoma cells was investigated. Spleen cells from W/Fu rats immunized with the syngeneic (C58NT)D tumor proliferate and generate cytotoxic potential for tumor targets after exposure to mitomycin C-treated (C58NT)D cells in vitro. Elimination of proliferating cells by exposure to high specific activity ³H thymidine at appropriate intervals impaired the generation of cytotoxic activity. Elimination of cells proliferating to either syngeneic lymphoma or BN rat alloantigens allowed the remaining cells to generate cytotoxic potential to the second set of antigens. Elimination of proliferating cells also abrogated the ability of the in vitro generated cells to adoptively confer anti-tumor protection on nonimmune recipients. These results demonstrate that cellular division is required for the generation of cells which are cytotoxic in vitro and can adoptively confer anti-tumor protection in vivo.

Footnotes

¹ This work was supported by Grants CA-19170 and CA-17481, awarded by the National Cancer Institute, Department of Health, Education, and Welfare.