Aerts-Toegaert Cindy, Heirman Carlo, Tuyaerts Sandra, Corthals Jurgen, Aerts Joeri L, Bonehill Aude, Thielemans Kris, Breckpot Karine
Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Brussels, Belgium.
Eur J Immunol. 2007 Mar;37(3):686-95. doi: 10.1002/eji.200636535.
Human CD83 is a marker molecule for mature dendritic cells (DC) and is also expressed on activated B and T cells. Although CD83 has been implicated in immune responses, its function on DC and T cells remains unclear. In this study, we wanted to assess the role of CD83 expressed on DC and T cells in the immune response. Down-regulation of CD83 expression on human DC through RNA interference (RNAi) results in a less potent induction of allogeneic T cell proliferation, reduced IFN-gamma secretion by established T cells and decreased capacity in the priming of functional tumor antigen-specific CD8+ T lymphocytes. In addition, CD83 mRNA-electroporated DC are stronger T cell stimulators. However, CD83 overexpression on Melan-A/MART-1-specific tumor-infiltrating lymphocytes (TIL) circumvents the need for CD83 expression on DC. Co-culture of immature DC with TIL or K562 cells overexpressing CD83 results in the production of enhanced levels of pro-inflammatory cytokines, whereas this production is less pronounced or even absent in co-cultures with non-modified TIL or K562 cells. In conclusion, we demonstrate that CD83 expression on T cells and DC modulates the immune response by activating DC and by delivering costimulatory signals for the stimulation of naive and memory T cells, respectively.
人CD83是成熟树突状细胞（DC）的标志物分子，在活化的B细胞和T细胞上也有表达。尽管CD83与免疫反应有关，但其在DC和T细胞上的功能仍不清楚。在本研究中，我们想评估DC和T细胞上表达的CD83在免疫反应中的作用。通过RNA干扰（RNAi）下调人DC上CD83的表达会导致异体T细胞增殖的诱导作用减弱，已建立的T细胞分泌的IFN-γ减少，以及功能性肿瘤抗原特异性CD8+ T淋巴细胞启动能力下降。此外，经CD83 mRNA电穿孔的DC是更强的T细胞刺激剂。然而，在黑色素瘤-A/MART-1特异性肿瘤浸润淋巴细胞（TIL）上过表达CD83可避免DC上对CD83表达的需求。未成熟DC与过表达CD83的TIL或K562细胞共培养会导致促炎细胞因子水平升高，而在与未修饰的TIL或K562细胞共培养时，这种产生不太明显甚至不存在。总之，我们证明T细胞和DC上的CD83表达分别通过激活DC和为刺激幼稚和记忆T细胞传递共刺激信号来调节免疫反应。
