Suppression of apoptosis in a cytotoxic T-cell line by interleukin 2-mediated gene transcription and deregulated expression of the protooncogene bcl-2

Ge Deng, Eckhard R. Podack

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171 Scopus citations

Abstract

Absence of interleukin 2 (IL-2) from IL-2-dependent cells, such as the cytotoxic T-cell line CTLL2, causes DNA fragmentation and programmed cell death (apoptosis). We found that, upon initiation, DNA degradation proceeds rapidly. IL-2-deprived CTLL2 cells can be rescued from apoptosis by the addition of IL-2 2 h prior to the onset of detectable DNA breakdown. Addition of inhibitors of transcription with IL-2 abolished the IL-2-mediated rescue of CTLL2 cells. Thus it appears that IL-2-mediated gene transcription is necessary for survival. Deregulated expression of a protooncogene, bcl-2, inhibits apoptosis of cells dependent on other hematopoietic growth factors. To determine whether bcl-2 was active in CTLL2 cells, we transfected CTLL2 cells with a plasmid containing bcl-2 cDNA expressed under the metallothionein promoter and observed prolonged survival of the transfected cells upon IL-2 deprivation. Cell growth, however, was arrested in the G0/G1 or G2/M phases of the cell cycle. The prolonged survival of bcl-2 transfectants allowed the analysis of endogenous bcl-2 mRNA levels by Northern blot analysis. The expression of endogenous bcl-2 was down-regulated within 8 h of IL-2 withdrawal and was not detected after 3 days. Addition of IL-2 induced endogenous bcl-2 expression within 8 h. Full recovery of bcl-2 expression was achieved by 24 h after IL-2 addition. We conclude that the survival of death-prone CTLL2 cells may be viewed as IL-2-dependent suppression of suicide, probably by the IL-2-induced expression of the cellular bcl-2 gene.

Original languageEnglish (US)
Pages (from-to)2189-2193
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number6
DOIs
StatePublished - Mar 15 1993

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