Correlation Between Natural and Antibody-Dependent Cell-Mediated Cytotoxicity Against Tumor Targets in the Mouse. I. Distribution of the Reactivity

Abstract

Direct comparison of natural killer (NK) activity against mouse tumor cells and antibody-dependent cell-mediated cytotoxicity (ADCC) against mouse tumor target cells coated with alloantisera indicated that the effector cells shared similar distribution patterns and had similar characteristics. The same lymphoid cell populations were tested simultaneously for NK activity and for ADCC. For ADCC, an 18-hour ⁵¹Cr release cytotoxicity assay was used. All the characteristics of the NK activity were the same regardless of whether the ⁵¹Cr release assay was performed for the usual 4 hours or for 18 hours. The levels of NK and ADCC reactivities of individual mice fluctuated in parallel; i.e., animals with high or low NK activity had correspondingly high or low ADCC. Peak activity for both functions occurred in mice between 5 and 9 weeks of age. Both effector activities were high in CBA and C3Hf mice and in several strains of nude mice, intermediate in C57BL/6 and BALB/c mice, and low in SJL mice. Organ distribution for both activities also correlated well, with the highest activities in cells from the spleen and peritoneal cavity, intermediate activities in cells from the lymph nodes and bone marrow, and the lowest activities in the cells from the thymus. Agents such as lymphocytic choriomeningitis virus that are capable of augmenting NK activity had a similar effect on ADCC. Conversely, when NK activity was depressed by the presence of murine sarcoma virus-induced tumors, ADCC was also depressed. Although the two effector functions produced synergistic results against target cells sensitive to NK, susceptibility to NK activity was not a prerequisite for susceptibility to ADCC; target cells resistant to NK activity could be lysed when they were coated with alloantibody.