CD83 expression on dendritic cells and T cells: Correlation with effective immune responses
CD83 expression on dendritic cells and T cells: Correlation with effective immune responses
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DOI：
10.1002/eji.200636535
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Breckpot, Karine
中科院分区：
文献类型：
--
作者：
Aerts-Toegaert, Cindy;Heirman, Carlo;Breckpot, Karine
人CD83是成熟树突状细胞（DC）的标记分子，并且也在活化的B和T细胞上表达。虽然CD83与免疫应答有关，但其在DC和T细胞上的功能仍不清楚。在这项研究中，我们希望评估DC和T细胞上表达的CD83在免疫应答中的作用。通过RNA干扰（RNAi）下调人DC上的CD83表达导致同种异体T细胞增殖的诱导效力降低、已建立的T细胞的IFN-γ分泌减少以及功能性肿瘤抗原特异性CD8（+）T淋巴细胞的引发能力降低。此外，CD83 mRNA电穿孔的DC是更强的T细胞刺激物。然而，Melan-A/MART-1特异性肿瘤浸润淋巴细胞（TIL）上的CD 83过表达避免了DC上CD 83表达的需要。未成熟DC与过表达CD83的TIL或K562细胞的共培养导致促炎细胞因子水平增加，而这种产生在与未修饰的TIL或K562细胞的共培养中不太明显或甚至不存在。总之，我们证明了T细胞和DC上的CD83表达通过激活DC和通过分别递送用于刺激幼稚和记忆T细胞的共刺激信号来调节免疫应答。
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. Coculture 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.