Mechanism of T cell‐mediated cytolysis: the differential impact of cytochalasins at the recognition and lethal hit stages

We have investigated the impact of a range of cytochalasins of various classes, not only on T cell‐mediated cytolysis as a whole, but also at each stage of this process using the analytical Ca ++ pulse method. We compared the results thus obtained with the effect of some of these drugs on microfilaments (assessed by electron microscopy) and on glucose metabolism. All cytochalasins blocked the recognition stage of T cell‐mediated cytolysis, none blocked the target cell disintegration stage, and all cytochalasins but cytochalasin A blocked Ca ++ ‐dependent events of the lethal hit stage. Cytochalasin A, which did not block lethal hit, clearly affected microfilaments. Cytochalasin B blocked both the lethal hit and glucose catabolism while cytochalasin A inhibited neither. The following pattern is therefore suggested. The recognition stage can be blocked by both cytochalasin A and cytochalasin B, presumably through a common effect of these drugs on microfilamental structures. The lethal hit stage can be blocked by cytochalasin B but not by cytochalasin A, presumably through the impact of the former on cell membrane permeability to glucose. These results are discussed both in terms of their practical interest relative to the use of Ca ++ and cytochalasin A to probe lytic events, and in terms of the information they provide about metabolic steps and cell structures which could be involved in the lethal hit.