Inhibition of T cell‐mediated cytolysis by 2‐deoxy‐D‐glucose: dissociation of the inhibitory effect from glycoprotein synthesis

摘要

AbstractPrevious studies have established that T cell‐mediated cytolysis can be reversibly inhibited by the hexose analogue 2‐deoxy‐D‐glucose (2‐DG) by a mechanism which is apparently unrelated to energy depletion. The possibility that the inhibitory effect of 2‐DG on cytolysis was linked to its known inhibitory effect on glycoprotein synthesis was therefore investigated. In contrast to the results obtained with 2‐DG, no inhibition of cytolysis was observed in the presence of tunicamycin, a potent and specific inhibitor of lipid carrier‐dependent protein glycosylation. Furthermore, populations of cytolytic cells which had been pretreated with doses of tunicamycin sufficient to block the incorporation of mannose (or 2‐DG) into glycoproteins were still fully susceptible to inhibition by 2‐DG. Other known inhibitors of viral protein glycosylation, such as glucosamine and galactosamine, inhibited cytolysis only weakly under conditions where 2‐DG was highly effective. Kinetic studies revealed that the inhibitory effect of 2‐DG on cytolysis could be reversed within minutes by the addition of exogenous glucose. Furthermore, suggestive evidence was obtained that inhibition of cytolysis by 2‐DG was linked to a parallel inhibition of effector: target cell binding. Taken together, these results strongly suggest that the inhibitory effect of 2‐DG on cytolysis can be dissociated from its effect on protein glycosylation. An alternative mechanism of