Loss of tumorigenicity following in vitro MuLV infection is associated with induction of peritoneal natural killer cell activity.

Infection by an attenuated replication-competent murine retrovirus (Friend leukemia virus-FLV4), but not other non-transforming retroviruses, stimulated rejection of transplantable thymomas (RL-cell line) and subsequent tumor immunity in syngeneic mouse recipients. FLV-infected RL-cells (RL-FLV) were unaltered in their in vitro growth, and grew progressively to kill sublethally irradiated animals and nude mice. Primary RL-FLV rejection was due to induction of increased natural killer (NK)-cell activity limited to peritoneal sites of tumor inoculation with a minor cytolytic macrophage population. Syngeneic mutant beige (NK-deficient) mice similarly rejected RL-FLV cells with increased peritoneal NK-cell activity and acquired immunity to the parental RL-tumor. While RL-FLV stimulated far greater peritoneal NK activity than did other tested retrovirus-infected RL-cells, the inherent susceptibility of these cells to lysis by normal NK cells was not altered by virus. RL-FLV induced NK effectors showed an indiscriminate lysis pattern that was independent of target cell type and retrovirus expression.