Development of a Murine Lymphoma Model System for the Characterization of Natural Killer.Tumor Cell Interactions1

We have developed a model system which can be utilized for charac terizing both the molecular basis of natural killer (NK):tumor interac tions and the consequences of these interactions on tumor growth in rivo. This model system consists of several tumor lines which were derived from the murine lymphoma ASLlw under conditions which permitted the isolation of clonal lines that differ in their susceptibility to NK-mediated lysis. The NK-resistant clones used in this study (AW5J and AW5E) were susceptible to cytotoxic T-lymphocyte-mediated lysis and thus appear to be resistant to lytic processes utilized uniquely by NK cells. In competitive (cold target) inhibition assays, the AW5J clone did not inhibit NK recognition as well as the NK-sensitive clones. Thus AW5J may not be efficiently recognized by NK cells. The AVV5E clone, on the other hand, competitively inhibited NK recognition as efficiently as the NK-sensitive clones; therefore, AYV5E appears to evade a postrecognition event which is required for NK-mediated lysis. The suscep tibility of these clones to killing by NK cells directly correlated with their lethality, suggesting that NK cells regulated the growth of these tumors in vivo. The level of host NK activity was also an important determinant of the level and site of tumor localization. Two-step inumi nofluorescence assays and flow cytometric analysis were used to quantitate the number of tumor cells in the bone marrow, spleen, and lymph nodes of mice with augmented or depleted NK activity. Increasing host NK activity decreased the number of tumor cells in each organ which could support the growth of the particular tumor tested. Furthermore, the extent of NK regulation was dependent, in part, upon the suscepti bility of the particular tumor to NK-mediated lysis and the site of tumor growth. Thus, the data presented here demonstrate the utility of the ASLlw-derived clones as a model system which can be used to delineate the requirements and consequences of NK:tumor interactions.