Journal of Experimental Medicine, Vol 146, 710-719, Copyright © 1977 by Rockefeller University Press
Energy metabolism and T-cell-mediated cytolysis. II. Selective inhibition of cytolysis by 2-deoxy-D-glucose
HR MacDonald
The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on T-cell-
mediated cytolysis has been investigated. 2-DG inhibited cytolysis in
glucose-free medium but not in medium containing equimolar concentrations
of glucose. This inhibition was reversible and quantitatively competitive
with glucose. Among other natural sugars examined, only mannose competed
effectively with 2-DG and reversed the inhibition of cytolysis, whereas
sodium pyruvate, fructose, galactose, fucose, and glucosamine were without
effect. Mannose and glucose were equally effective in competing with 2-DG
on a molar basis. When other glucose analogues such as 5-thio-D-glucose
(5-SH-G) and 3-O- methylglucose were investigated under the same
conditions, no inhibition of cytolysis was observed however, 5-SH-G (but
not 3-O- methylglucose) was able to reverse the inhibitory effect of 2-DG
in a competitive fashion. Taken together with the data presented in the
accompanying paper, these findings provide strong evidence that 2-DG
inhibits T-cell-mediated cytolysis by a mechanism that is unrelated to
energy production. The possibility that inhibition is related to
interference with membrane glycoprotein synthesis is discussed.
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