Cell-mediated Immunity to Leukemia Virus- and Tumor-associated Antigens in Mice

Cell-mediated immune reactions appear to play an important role in resistance against growth of leukemia cells in mice. Possible mechanisms for in v ivo protect ion in two tumor systems are discussed. These tumor models, which are a Friend leukemia virus-induced transplantable tumor, FBL-3, and primary murine sarcoma virus (MSV)-induced tumors, are strongly antigenic; under some condit ions, tumors regress completely. In mice with regressing FBL-3 tumors, cell-mediated cytotoxicity was measured by release of [l=51]iododeoxyuridine. The response was biphasic, with an initial peak at 10 days and a 2nd peak after 30 days. A boost in reactivity could be elicited by later challenge with tumor cells. All of the reactivity was dependent on T-cells, being el iminated by treatment with anti-0 plus complement. The specif icity of the reactions was not completely defined, but it was consistent with Friend type-specif ic antigen plus broader, common antigens. In mice with regressing MSV tumors, strong cell-mediated cytotoxicity, measured mainly by release of '~'Cr, was seen against RBL-5, a Rauscher virus-induced leukemia. A single peak of response occurred at about 14 days after virus inoculat ion. Upon later challenge with RBL-5 cells, a vigorous and rapid secondary response was elicited, mainly in the region of tumor challenge. This cytotoxic reactivity also was completely dependent on T-cells. In addit ion, macrophage-mediated inhibi t ion of leukemia cell growth in v i t ro was seen in this system at the time of peak tumor development. The '~Cr release cytotoxicity was specif ic and directed primari ly against an antigen, MEV-SA1, associated with mouse endogenous C-type viruses. The macrophage-induced growth inhibi t ion appeared to be nonspecif ic. In both the FBL-3 and MSV tumor systems, protect ion against tumor growth could be adoptively transferred by immune lymphoid cells. In addit ion to induction of cell-mediated immunity by tumor cell or virus inoculation, cell-mediated cytotoxic reactivity was found to occur naturally in most young mice. This natural kil ler activity was quite dist inct from the experimental ly elicited reactions, being mediated by N-cells, a subpopulat ion of lymphoid cells wi th no clearly identif iable cell surface markers. The natural cytotoxici ty was also directed against ant igenic specificit ies different from those recognized by the MSVimmune cells. The central issue in all of these studies has