Characteristics of immunity induced by neuraminidase-treated lymphosarcoma cells in C3H (MTV+) and C3H (MTV-) mice.
The immunogenicity of 6C3HED lymphosarcoma ascites tumor cells was greatly enhanced upon treatment with Vibrio cholerae neuraminidase. As a result, mammary tumor virus (MTV)-free C3H mice which had been repeatedly immunized with the treated cells resisted a challenge of 10(6) untreated viable cells inoculated i.p., whereas all control animals died after receiving less than 10 lymphosarcoma tumor cells. In contrast, there was no increase in the refractoriness to challenge when MTV-infected C3H mice were immunized. Incubation of 6C3HED lymphosarcoma cells with serum of splenic lymphocytes from the immunized MTV-free C3H mice neutralized their tumorigenicity and protected recipient MTV-free and MTV-infected C3H mice against the disease. As shown by the 51Cr microcytotoxicity assay, the complement-dependent cytotoxic antibody titer reached 1,024; 29% of the target cells were lysed by lymphocytes obtained from immune MTV-free C3H mice. When the immune lymphocytes were pretreated with anti-theta serum they lost their ability to neutralize the tumorigenicity of the lymphosarcoma, failed to be stimulated by the T cell mitogens, phytohemagglutinin and concanavalin A, and failed to achieve cytolysis of the lymphosarcoma target cells in vitro. These observations establish the central role of the theta-antigen-bearing immune lymphocytes in cell-mediated immunity in this system. Failure of the immune system in the immunized MTV-infected C3H mice to cope with the challenging lymphosarcoma, even at low cell numbers, was reflected, not in the absence of humoral response, but in the relatively low level of cell-mediated immunity. This was manifested in both the neutralization and in the vitro cell-mediated immunity assays. This apparent immunological deficiency observed in the MTV-infected C3H mice could be countered by the transfer of lymphocytes from MTV-free C3H mice immunized with neuraminidase-treated 6C3HED lymphosarcoma cells. The recipient MTV-infected C3H mice then rejected a subsequent challenge with lymphosarcoma tumor grafts.