NF-kappaB-dependent regulation of the timing of activation-induced cell death of T lymphocytes.
One of the mechanisms by which activated T cells die is activation-induced cell death (AICD). This pathway requires persistent stimulation via the TCR and engagement of death receptors. We found that TCR stimulation led to transient nuclear accumulation of the NF-kappaB component p65/RelA. In contrast, nuclear c-Rel levels remained high even after extended periods of activation. Loss of nuclear p65/RelA correlated with the onset of AICD, suggesting that p65/RelA target genes may maintain cell viability. Quantitative RNA analyses showed that three of several putative NF-kappaB-dependent antiapoptotic genes were expressed with kinetics that paralleled nuclear expression of p65/RelA. Of these three, ectopic expression only of Gadd45beta protected significantly against AICD, whereas IEX-1 and Bcl-x(L) were much less effective. We propose that the timing of AICD, and thus the length of the effector phase, are regulated by transient expression of a subset of p65/RelA-dependent antiapoptotic genes.
Mittal
Akanksha
A
Rosensteil Research Center and Department of Biology, Brandeis University, Waltham, MA 02454, USA.
Papa
Salvatore
S
Franzoso
Guido
G
Sen
Ranjan
R
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
D016328:NF-kappa B; C498144:Rela protein, mouse; D051996:Transcription Factor RelA