T cell-mediated cytolysis: on the strength of effector-target cell interaction

Allosensitized lymphoid cell populations contain T lymphocytes that can bind to target cells and lyse them. We asked whether there was a relationship between lymphocyte target cell-binding strength and occurrence of cytolysis. Using graded shear forces to dissociate effector-target cell conjugates, we found that (a) within an allosensitized lymphoid cell population derived from an heterogeneous mixed leukocyte culture, there were lymphocyte-target cell conjugates with binding strengths differing by a factor of at least 10(2), (b) even the minimal force required to release a significant amount of bound target cells could disrupt the plasma membranes of some tumor cells and (c) these tumor cells disrupted by shear forces were probably part of cytolysis-conducive rather than of non-cytolysis-conductive conjugates. We combined this approach with the use of cytolysis-inhibiting monoclonal antibodies (mAb), and found that antibody-induced decrease of cytolysis was correlated with a decrease in the percentage of strong or total conjugates, depending on the mAb used. When lectins were added to overcome the inhibitory effect of the mAb, reappearance of cytolytic activity correlated with reappearance of conjugates. This was especially striking using wheat germ agglutinin (WGA): the addition of WGA to irrelevant effector-target cell combinations did not lead to cytolysis; however, the addition of WGA to relevant effector-target cell combinations inhibited by mAb led to reappearance of cytolysis and of strong conjugates. Taken together, these and other results suggested that under our experimental conditions a threshold level of binding strength between effector and target cells might be important, although not sufficient, for T cell-mediated cytotoxicity. These results were not inconsistent with the involvement of mechanical factors in this process. Also, they were in line with the concept of nonantigen-specific lymphoid cell surface interacting molecules, detected by the mAb used and important for the establishment of strong, functional lymphocyte target cell interactions. Finally, they underlined the necessity of a quantitative estimate of cell-cell binding strength when investigating the effect of a given agent (e.g. a mAb) on lymphocyte target cell recognition.