STUDIES ON MECHANISM OF LYMPHOCYTE-MEDIATED CYTOLYSIS .8. USE OF CON A TO DELINEATE A DISTINCTIVE KILLER T CELL SUBPOPULATION

Abstract

Alloimmune spleen cells (C57BL/6 anti-[mouse mastocytoma]P815), but not normal spleen cells, lyse syngeneic([leukemia] EL4) target cells in the presence of Con A [concanavalin A]. Con A dependent cytotoxicity was mediated by T [thymus-derived] cells and required the continued presence of lectin. Cytolysis in the presence of a succinylated derivative was equivalent to that seen with the parent Con A molecule. Lysis is not primarily caused by directly cytotoxic T cells. The reasons for this conclusion are as follows: removal of directly cytotoxic cells by adsorption on P815 monolayers did not alter the Con A dependent cytolysis of EL4 cells; populations in which no direct T killers were demonstrable (e.g., spleen cells harvested 5 days after alloimmunization) lysed P815 and EL4 cells in the presence of Con A; and Con A dependent cytolysis, but not direct cytotoxicity, could be induced by culturing normal C57BL/6 spleen cells for 4 days with a sonicated extract of P815 cells. The cell activated to lyse targets in the presence of Con A is apparently a T cell which has differentiated lytic potential following alloantigenic stimulation, but has insufficient density or affinity of antigen receptors to serve as a directly cytotoxic cell. The role of Con A is apparently to bridge killer and target cell and to activate the effector.