Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic target cells.

The levels of natural cell-mediated cytotoxicity against tumor cells in young BALB/c and BALB/c nude mice could be augmented by inoculation of a variety of mouse tumor cells or of mouse thymocytes. In older mice with low levels of spontaneous cytotoxic reactivity, inoculation of tumor cells led to rapid appearance of cytotoxicity. This augmented cytotoxicity reached a peak 3 days after inoculation and then declined rapidly. The specificity of the augmented cytotoxicity appeared to be the same as that seen with natural cell-mediated cytotoxicity. The detected antigens were restricted to mouse tumor cells and thymocytes, and were absent on cells from other species. The effector cells after boosting also had the same cell surface characteristics as the natural cytotoxic effector cells, being non-adherent, non-phagocytic, and only weakly sensitive to treatment with anti-theta serum plus complement. In addition to this boosting by mouse tumor cells, marked increases in the levels of cytotoxicity were caused by a variety of murine viruses, including murine sarcoma virus and lymphocytic choriomeningitis virus. These effector cells also had the same properties as those seen with natural cytotoxic effector cells. The results indicate that the levels of natural cell-mediated cytotoxicity in conventional and athymic BALB/c mice can be consistently and rapidly boosted by inoculation with tumor cells or viruses. This should provide a valuable tool for better understanding of the mechanisms responsible for the expression of natural cytotoxicity and its relevance to in vivo resistance to tumor growth.