Gasparini Chiara, Foxwell Brian M J, Feldmann Marc
Kennedy Institute of Rheumatology Division, School of Medicine, Imperial College London, London, UK.
Eur J Immunol. 2009 Aug;39(8):2215-23. doi: 10.1002/eji.200939209.
DC, when fully matured are the APC best able to activate naïve T cells. Recently, we demonstrated using adenoviruses overexpressing IkappaBalpha and proteosome inhibitors that NF-kappaB is involved in DC activation, but the role of the individual subunits is still not clear. We investigated the role of the NF-kappaB subunits RelB and p50 in human DC activation using adenoviral vectors expressing RelB or p50. Nuclear RelB, in the form of RelB/p50, was active only in DC infected with both viruses, this induced the production of the soluble homeostatic chemokine CCL19, but not other homeostatic chemokines, particularly in LPS-matured DC. However, RelB/p50 did not affect the expression of costimulatory and antigen-presenting molecules, and increased the allogeneic mixed lymphocyte reaction only in LPS-matured DC. This enhanced mixed lymphocyte reaction is most likely due to enhanced CCL19 production, which sustains the interaction between mature DC and naïve T cells. In conclusion, we demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation.
成熟后的树突状细胞(DC)是最能激活初始T细胞的抗原呈递细胞(APC)。最近,我们通过使用过表达IkappaBalpha的腺病毒和蛋白酶体抑制剂证明,核因子-κB(NF-κB)参与DC的激活,但其各个亚基的作用仍不清楚。我们使用表达RelB或p50的腺病毒载体研究了NF-κB亚基RelB和p50在人DC激活中的作用。以RelB/p50形式存在的核RelB仅在同时感染两种病毒的DC中具有活性,这诱导了可溶性稳态趋化因子CCL19的产生,但不诱导其他稳态趋化因子的产生,特别是在脂多糖(LPS)成熟的DC中。然而,RelB/p50不影响共刺激分子和抗原呈递分子的表达,并且仅在LPS成熟的DC中增强了同种异体混合淋巴细胞反应。这种增强的混合淋巴细胞反应很可能是由于CCL19产生增加,从而维持了成熟DC与初始T细胞之间的相互作用。总之,我们证明RelB/p50仅在同时表达RelB和p50的DC中具有活性,并诱导CCL19的产生,但不诱导DC成熟。