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Abstract
The mechanism by which the transient adhesion between cytotoxic T-lymphocytes (Tc) and specific target-cells induces lysis of the latter, is still controversial. Techniques of quantitative cytochemistry, adapted for use on isolated cells, have been used to test the hypothesis that the Tc acting solely on the surface of its particular target-cell, produces such metabolic changes within the target-cell as to lead to its lysis. Almost complete loss of lysosomal bound naphthylamidase activity occurred in specific target-cells 15 min after adhesion of Tc. Such loss of lysosomal membrane integrity was induced, in the absence of Tc, by spermidine. This suggested that the adhesion of Tc to the specific target-cells activated the polyamine synthesis pathway in the latter. Evidence supporting this view was the finding that shortly after adhesion of Tc, there was appreciable increase in glucose 6-phosphate dehydrogenase (G6PD) activity within the target-cells, seeing that G6PD can be activated by putrescine, the immediate product of ornithine decarboxylase (ODC) activity. Moreover, both the changes in lysosomal membrane integrity and the G6PD stimulation were inhibited when the interaction was done in the presence of the ODC-inhibitor. Furthermore, the application of a newly developed quantitative cytochemical method confirmed that ODC activity was stimulated very early after adhesion of the Tc. Finally, when the interaction between the Tc and the target-cells was done in the presence of the ODC-inhibitor, target-cell lysis, as assessed by the chromium-release assay, was virtually abolished at concentrations of the inhibitor greater than 20 mM. Thus it seems that the interaction of the Tc with its specific target-cell, by perturbing the target-cell plasma membrane, elevates ODC acitivity, which, when sufficient, could produce enough spermidine to labilize completely the lysosomal membrane.
