Mondor I, Schmitt-Verhulst A-M, Guerder S
Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique/Université de la Méditerranée, Parc Scientifique de Luminy, Marseille, France.
Cell Death Differ. 2005 Nov;12(11):1398-406. doi: 10.1038/sj.cdd.4401673.
Nuclear factor of kappa B (NF-kappaB) transcription factors are critical regulators of T-cell activation and survival. The relative contribution of individual NF-kappaB members to these processes remains elusive. We investigated the role of RelA in the regulation of CD8 T-cell activation. We overexpressed, in mature CD8 T cells, a transactivation domain-deficient RelA molecule (p65TAD). We show that p65TAD forms homo- and heterodimers with p50 that bind kappaB sites and selectively inhibit RelA-dependent transactivation. Expression of p65TAD does not affect initial activation or cell cycle progression but induces the death of activated CD8 T cells in vitro and in vivo. However, the long-term survival of resting effector CD8 T cells seems not to be affected by p65TAD expression. Collectively, our results indicate that RelA is a critical regulator of survival of proliferating CD8 T cells but may be dispensable for the survival of resting effector T cells.
核因子κB（NF-κB）转录因子是T细胞活化和存活的关键调节因子。单个NF-κB成员对这些过程的相对贡献仍不清楚。我们研究了RelA在调节CD8 T细胞活化中的作用。我们在成熟的CD8 T细胞中过表达了一种转录激活结构域缺陷的RelA分子（p65TAD）。我们发现p65TAD与p50形成同源二聚体和异源二聚体，它们结合κB位点并选择性抑制RelA依赖性转录激活。p65TAD的表达不影响初始活化或细胞周期进程，但在体外和体内诱导活化的CD8 T细胞死亡。然而，静止效应CD8 T细胞的长期存活似乎不受p65TAD表达的影响。总体而言，我们的结果表明RelA是增殖性CD8 T细胞存活的关键调节因子，但对于静止效应T细胞的存活可能是不必要的。
