MECHANISM OF CELL-MEDIATED CYTOTOXICITY AT THE SINGLE CELL LEVEL .2. EVIDENCE FOR 1ST-ORDER KINETICS OF T-CELL-MEDIATED CYTOLYSIS AND FOR HETEROGENEITY OF LYTIC RATE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 123  (6) , 2870-2877
Abstract
Kinetics and rate of T [thymus-derived] cell-mediated cytolysis was assessed by measuring times required for lysis of isolated target cells by single cytotoxic lymphocytes. Single target cell lysis was determined microscopically by observing trypan blue uptake as a function of time of incubation of effector-target conjugates in agarose. Lysis of EL-4 [mouse lymphoma] target cells by alloimmune peritoneal exudate lymphocytes was initiated without a lag and was essentially complete at 2 h. Zero-order and 1st-order kinetics equations were analyzed for fit to the O-2 h lysis values. Statistically, the zero-order kinetic function could be rejected (P > 0.05), but the 1st-order kinetics function (P < 0.01) could not. Within each CTL-target cell population, cytolysis probably occurs exponentially as a random decay process. One event in the entire process of cytolysis is probably rate limiting. The 1st-order equation was applied to measurements of the rate of cytolysis in many different individual effector-target cell combinations. Significant differences in lytic rate were apparent when the effector or target cells were varied, with the rate constants spanning a 5-fold range. Heterogeneity of lytic rates indicates that lytic efficiency is a function of effector and target cells used.

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