The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Journal of Experimental Medicine, Vol 175, 23-27, Copyright © 1992 by Rockefeller University Press

ARTICLES

Inhibition of cytotoxic T lymphocyte-induced target cell DNA fragmentation, but not lysis, by inhibitors of DNA topoisomerases I and II

WK Nishioka and RM Welsh
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.

Cytotoxic T lymphocytes (CTL) kill their target cells via a contact- dependent mechanism that results in the perturbation of the target cell's plasma membrane and the fragmentation of the target cell's DNA into nucleosomal particles. The membrane disruption is presumed to be due to the action of perforin, while the DNA fragmentation is thought to be by the activation of an endogenous nuclease(s). DNA topoisomerases I and II are nuclear enzymes with inherent endonuclease activities. We have investigated their role in the CTL-induced DNA fragmentation process. We report that in CTL killing assays, the treatment of target cells with topoisomerase I and II inhibitors blocks the CTL-induced DNA fragmentation process, but not the lysis of the target cell.
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