DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death

Cheryl D. Helgason, Lianfa Shi, Arnold H. Greenberg, Yufang Shi, Peter Bromley, Thomas G. Cotter, Douglas R. Green, R. Chris Bleackley

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Cytotoxic T lymphocyte (CTL)-mediated lysis is accompanied by fragmentation of target cell DNA into an oligonuclcosome ladder, a hallmark of apoptosis. Is this a fortuitous coincidence, or could CTL be inducing lysis by activation of the suicide signal? In this report we demonstrate that CTL-mediated target cell death can be blocked with the drug aurintricarboxylic acid (ATA). The abrogation of death correlates with the inhibition of DNA fragmentation. While ATA prevented DNA fragmentation, it failed to significantly alter protein, RNA, or DNA synthesis in the cell lines over the dose range used. In addition, there was no inhibition of cell-cell interaction or granule exocytosis during CTL-mediated killing. ATA also significantly inhibited the cytolysis and DNA fragmentation mediated by isolated cytolytic granules, as well as the granular protein fragmentin. We developed an assay in which target cells could be separated from CTL after binding and programming for lysis. Once they had received the “kiss of death,” target cells could be rescued from lysis (as indicated by inhibition of DNA fragmentation and increased target cell viability) by treatment with ATA. These results suggest that ATA blocks target cell death by inhibition of DNA fragmentation, and further, that chromatin degradation is a cause rather than a result of cell death in CTL-mediated lysis.

Original languageEnglish (US)
Pages (from-to)302-310
Number of pages9
JournalExperimental cell research
Volume206
Issue number2
DOIs
StatePublished - Jun 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint

Dive into the research topics of 'DNA fragmentation induced by cytotoxic T lymphocytes can result in target cell death'. Together they form a unique fingerprint.

Cite this