The role of lectin in lectin-dependent cell-mediated cytolysis has been pursued by using alloimmune C57BL/6 spleen cells as a source of effector cells and EL4 lymphoma cells, syngeneic to the effector, as targets. Of a variety of lectins studied, in this system, only the T cell mitogens concanavalin A (Con A), Lens culinaris hemagglutinin A, and leucoagglutinin derived from phytohemagglutinin were able to support cytolysis. Agglutinating agents that were not mitogenic, such as wheat germ agglutinin or antisera against the interacting cells, did not promote cytolysis. B cell mitogens were similarly unable to support lysis even when co-incubated with agglutinating agents.
The role of the T cell mitogens in lectin-dependent cytolysis appeared to be 2-fold: “activation” of the effector cell to express its cytotoxic potential and “bridging” of the effector cell to its target. These conclusions were based on the findings that: a) agglutination of target cells to T effector cells, although necessary to elicit cytolysis, was in itself insufficient, and b) T cells “activated” by mitogen under conditions which precluded cell-cell bridging did not lead to lysis.
Furthermore, we could find no evidence that the bridging function of the lectin during cytolysis could be served by agents other than T cell mitogens. This might explain our finding that the Ca++ ionophore A23187, which others have shown to substitute for Con A in the early stages of a mitogenic response, but which does not cause cell agglutination, did not mediate cytolysis, even in the presence of nonmitogenic agglutinins.
These findings of stringent requirements for both the “activating” and “bridging” roles of lectin during cytolysis necessitate radical revision of previous notions that the lectins serve merely as a “glue.”