Prearmed effector cells and the target cell specificity of lectin-induced cellular cytotoxicity

We have investigated mechanisms by which plant lectins induce human peripheral blood mononuclear cells to kill red blood cells (RBC) from different species selectively. Cytotoxicity was induced by both mitogenic components of phytohemagglutinin-P (PHA), erythroagglutinating (E-PHA) and leukoagglutinating (L-PHA), and the nonmitogenic lectin wheat germ agglutinin (WGA). The target cells used in an overnight chromium release assay included human autologous RBC, human allogeneic RBC, and xenogeneic RBC from sheep or chickens. Although E-PHA induced cytotoxicity for all cell types, L-PHA caused human mononuclear cells to kill only xenogeneic RBC and, conversely, WGA induced killing of only human RBC. These differences allowed further investigation of possible control mechanisms. The target cell specificity associated with lectin-induced cellular cytotoxicity did not correlate with lectin binding to, or agglutination of, the different red blood cell types. Furthermore, preincubation of RBC with lectins followed by washing did not result in cytotoxicity. However, when the mononuclear cells were preincubated with the lectins, the same cytotoxic specificity was observed as when lectins were present during the entire assay. These experiments suggest that the target cell specificity observed with lectin-induced cellular cytotoxicity is related to a prearmed lymphocyte which seeks out and kills the appropriate target cell.