In vitro generation of cytotoxic lymphocytes against radiation and radiation leukemia virus-induced tumors - I. Role of viral antigenicity

Cytotoxic T lymphocytes (CTL) to syngeneic radiation- or radiation leukemia virus (RadLV)-induced tumors were generated in vitro in mixed lymphocytetumor cultures (MLTC) using splenocytes of mice primed in vivo with inactivated tumor cells. Effective sensitization was obtained with virus-producer cell lines, while cells of a virus-nonproducer line did not sensitize. The CTL could lyse syngeneic, but not allogeneic, tumor cells of established lines producing C-type virus and therefore expressing membrane-associated viral antigenicity. Susceptibility of primary leukemias to cell-mediated lysis could not be tested due to a very high spontaneous ⁵¹Cr release shortly after labeling. In a cold target competition assay, however, the RadLV-induced, but not the X-radiation-induced primary tumor cells inhibited the cytotoxic reactivity. This inhibition was correlated with the level of viral antigen expression on the inhibiting cells, which was high in the RadLV-induced and low in the radiation-induced primary tumors. These results suggest that antitumor CTL generated under conventional MLTC conditions are largely stimulated by and directed at virus-related antigens not necessarily associated with the malignant state of the cell.