Lectin-induced nonlethal adhesions between cytolytic T lymphocytes and antigenically unrecognizable tumor cells and nonspecific “triggering” of cytolysis.

The demonstration of nonlethai adhesion between a cytolytic T lymphocyte (CTL) and a target cell would indicate that adhesive contact with a CTL is insufficient for target cytolysis. For this reason, several lectins were tested for their ability to induce either of two types of interactions between alloimmune CTL and antigenically unrecognizable (nonspecific) target cells: 1) lethal adhesions, leading to cytolysis of the target cell (lectin-dependent nonspecific lysis, or LNL), and 2) adhesions that do not lead to lysis of the target cell. Of the lectins that caused LNL, some, including wheat germ agglutinin (WGA), phytohemagglutinin, castor bean agglutinin, and concanavalin A (Con A), produced a significant degree of nonlethai adhesion under appropriate conditions; others, including Wellcome purified phytohemagglutinin and pokeweed mitogen, did not produce nonlethai adhesion. One lectin, soybean agglutinin, caused little LNL but did produce substantial nonlethai adhesion. Asparagus pea lectin caused neither LNL nor nonlethai adhesion. The data are consistent with the hypothesis that a lesser concentration of lectin is required for the mediation of nonlethai adhesion than for the production of lethal adhesion and LNL. A new assay, called post-dispersion lectin-dependent nonspecific lysis (PDLNL) was developed to quantitate the percentage of target cells nonlethally adhering to CTL. This assay depends upon both the formation of strong, shear-resistant effector-target cell adhesions, and intact function of the adhering CTL as reflected by their ability to kill adhering target cells upon the addition of Con A. After the production of nonlethai effector-target cell adhesions with WGA, PDLNL was shown to be a) dependent on Thy 1-bearing effector cells, and b) inhibited by drugs that inhibit T cell cytolysis, indicating a requirement for active cytolytic T lymphocytes. The nonlethai nature of the adhesions produced by WGA could not be accounted for by a) lack of persistence of the adhesions, b) failure of WGA to induce effector-target cell adhesions, c) an inhibitory effect of WGA, or d) inadequate intercellular contact. These observations provide the strongest evidence yet offered against the hypothesis that effector-target cell adhesion is sufficient for target cytolysis, and are compatible with a requirement for an additional “triggering” event to initiate the administration of a lethal hit by CTL adherent to target cells. The system described here provides an assay for future studies attempting to characterize such a “triggering” event.