Energy requirements of the binding and lytic steps of T lymphocyte-mediated cytolysis of leukemic cells in vitro

Abstract

The process of T lymphocyte-mediated destruction of target cells in vitro is temperature dependent and is suppressed by inhibitors of energy metabolism, but the energy requirements for the conjugation and lytic steps of the process are different. The conjugation step of lymphocytes and target cells is prevented by metabolic inhibitors and is dependent on temperature, increasing in the range from 2 degrees C to 22 degrees C. However, after lymphocyte-target cell conjugates are formed, they are stable at low temperatures (0 degree C) and in the presence of metabolic inhibitors. Thus, the formation but not the maintenance of lymphocyte-target cell conjugates is an energy-dependent process. In contrast to the conjugation step, which is influenced both by metabolic inhibitors and by temperature, the lytic step, which occurs only between 22 degrees C and 37 degrees C, is not affected by inhibitors of energy metabolism. The sigmoidal behavior of lysis as a function of temperature, showing a sharp inflection around 20 degrees C, can be explained in terms of the alteration of the viscosity of the membrane matrix of the target cells rather than as a general metabolic effect on the killer and target cells.