TY - JOUR
T1 - NF-κB-dependent regulation of the timing of activation-induced cell death of T lymphocytes
AU - Mittal, Akanksha
AU - Papa, Salvatore
AU - Franzoso, Guido
AU - Sen, Ranjan
PY - 2006/2/15
Y1 - 2006/2/15
N2 - 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-κB 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-K15-dependent antiapoptotic genes were expressed with kinetics that paralleled nuclear expression of p65/RelA. Of these three, ectopic expression only of Gadd45β protected significantly against AICD, whereas IEX-1 and Bcl-X, were much less effective. VVe 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.
AB - 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-κB 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-K15-dependent antiapoptotic genes were expressed with kinetics that paralleled nuclear expression of p65/RelA. Of these three, ectopic expression only of Gadd45β protected significantly against AICD, whereas IEX-1 and Bcl-X, were much less effective. VVe 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.
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M3 - Article
C2 - 16455974
AN - SCOPUS:32044462297
SN - 0022-1767
VL - 176
SP - 2183
EP - 2189
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -