PMID: 7537299May 15, 1995Paper

Lytic reaction of in vivo primed peritoneal exudate CTL. Induction of high-conductance single channels in the target cell membrane

The Journal of Immunology : Official Journal of the American Association of Immunologists
R LavyO Binah

Abstract

CTL, primary effectors in immune responses, deliver a "lethal hit" signal to target cells, causing their destruction. The precise membrane events associated with the lethal hit remain elusive. We investigated the signal(s) mediating destruction of tumor target cells (EL4) by perforin-deficient peritoneal exudate CTL (PEL). We utilized patch clamp techniques to record electrophysiological events associated with the cytolytic interaction of PEL and EL4 in isolated conjugates. PEL-EL4 interaction resulted in induction in EL4 cells, of single channels (followed by EL4 destruction), with a mean conductance of 437 pS and a reversal potential of -1.0 mV, suggestive of nonselective pathways. Similar channels were induced in EL4 cells conjugated with perforin-rich PEL blasts (PEB), by perforin, postnuclear extract from PEL (pnPEL) and from other cytotoxic lymphocytes, but not from noncytolytic lymphocytes. As similar channels were induced by pnPEL in EL4 membrane patches, we propose that these channels result from a direct effect of PEL-derived channel-forming substance(s) on the target cell's membrane. Importantly, postnuclear extracts from perforin-devoid cytotoxic PEL-hybridomas induced similar channels, suggesting the presence of a ...Continue Reading

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