Cytotoxic Activity of Human Lymphocytes: Quantitative Analysis of T Cell and K Cell Cytotoxicity, Revealing Enzyme-Like Kinetics

Abstract

Abstract The mechanism of action of human cytotoxic lymphocytes was studied in two systems: T cell cytotoxicity in cell-mediated lympholysis (CML) and K cell cytotoxicity in antibody-dependent lymphocytotoxicity (ADL). The mechanisms resemble that of an enzyme, if the effector cells are regarded as enzyme and the target cells as substrate. On the basis of a kinetic analysis it was shown that the experimental data are compatible with a simple rate equation, which allows the definition of three constants: p, representing the maximal killing rate of the effector cell suspension (at target →∞); q, representing the maximal lysis of the target cells (at effector →∞); K which represents the Michaelis constant (i.e, the target cell number giving ½ Vmax), when extrapolated to effector = 0. The constant K may be taken to reflect the affinity between effector and target cells. Furthermore, for the ADL system the influence of the effector cell concentration on Km was due not to the addition of inert cells but rather to the presence of cells that can bind but not kill. Finally, it was shown that in the ADL a K cell can recycle, i.e., kill more than one target cell. On the basis of these results, experimental conditions are proposed for optimal measurement of cellular cytotoxicity.