1997 Articles

Regulation of Fas-Dependent Activation-Induced T cell Apoptosis by cAMP Signaling: A Potential Role for Transcription Factor NF-κB

Ivanov, Vladimir N.; Lee, Richard K.; Podack, Eckhard R.; Malek, Thomas R.

TCR-mediated activation of T cell hybridomas induces programmed cell death by a Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the absence or presence of transgenic Bcl-2, with anti-CD3epsilon and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective down-regulation of the nuclear levels of NF-κB p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-κB activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-κB p65 antisense oligonucleotide down-regulated nuclear levels of NF-κB, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-κB in the regulation of activation-induced apoptosis in T lymphocytes.