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

Abstract:

:Cytotoxic T lymphocyte (CTL)-mediated lysis is accompanied by fragmentation of target cell DNA into an oligonucleosome 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.

journal_name

Exp Cell Res

authors

Helgason CD,Shi L,Greenberg AH,Shi Y,Bromley P,Cotter TG,Green DR,Bleackley RC

doi

10.1006/excr.1993.1150

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

302-10

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(83)71150-X

journal_volume

206

pub_type

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