Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. IV. Inhibition of programming for lysis by pharmacologic agents.

Abstract

The mechanism of T cell-mediated cytolysis has previously been resolved into three successive steps: adhesion formation, programming for lysis, and killer cell-independent lysis. In the present report we have examined the effects of a variety of drugs on programming for lysis. Concanavalin A (Con A)-coated specific target cells were incubated with effector cells at 37°C in the absence of Ca++so that adhesions could form under conditions that did not permit programming for lysis. Such adhesions were shown not to be detached by EDTA or by any of the drugs tested. After adhesion formation, Ca++and the drug of interest were added to the cultures, and the amount of ensuing lysis was measured. The following drugs were found to block programming lysis, either partially or completely: trypan blue, benzyl alcohol, lidocaine, dimethylsulfoxide, colchicine, cytochalasin B, dibutyryl cyclic AMP, sodium azide, heparin, and FPTP. Cytochalasin B, however, was shown to block programming for lysis with substantially less potency than adhesion formation. Attempts to demonstrate a sequence of inhibitable steps within programming for lysis were carried out with the following combinations of agents: all possible pairs of the four inhibitors EGTA, trypan blue, FDTP, and benzyl alcohol; EGTA and low temperature; EGTA and sodium azide plus 2-deoxy-D-glucose. No sequence of inhibitable steps was found. The possibility that many or most of the inhibitors studied in these experiments may impede programming for lysis by limiting the closeness of contact between effectors and targets is discussed.