Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral immunity in HBV transgenic mice
Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral immunity in HBV transgenic mice
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阻断 B7-H1 可增强 HBV 转基因小鼠中树突状细胞介导的 T 细胞反应和抗病毒免疫
DOI：
10.1016/j.vaccine.2011.11.076
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发表时间：
2012-01-17
期刊：
影响因子：
5.5
通讯作者：
Jiang, Wenzheng
中科院分区：
文献类型：
--
作者：
Jiang, Wenzheng
树突状细胞（Dendritic cells, dc）被认为是最有效的抗原呈递细胞（antigen-presenting cell， APC），在治疗癌症或慢性病毒感染的疫苗策略中，树突状细胞（Dendritic cells, dc）的应用备受关注。B7-H1 （PD-L1）是程序性细胞死亡-1 （PD-1）的配体，不与其他CD28家族成员结合，它在静止状态下表达，在活化的B细胞、T细胞、髓细胞和树突状细胞（dc）上表达上调。大量的研究支持B7-H1作为T细胞反应的负调节因子的作用。RNA干扰（RNAi）是一种通过双链RNA分子对基因表达进行序列特异性转录后抑制的机制，最近已被应用于哺乳动物细胞中，使用小干扰RNA （sirna）。在本研究中，用B7-H1基因特异性siRNA转染dc，可阻断dc上B7-H1的表达。抑制B7-H1可增强dc的异源刺激活性。在混合淋巴细胞反应（MLR）中，阻断dc的B7-H1可抑制ifn - γ和IL-10的产生，但不能抑制IL-2和IL-4的产生。HBV特异性肽脉冲dc可打破耐受性并引发特异性CTL反应，HBV转基因小鼠血清中HBsAg和HBV DNA水平下降，而阻断B7-H1对dc的作用增强。这些数据有力地支持了阻断B7-H1可以增强dc介导的抗病毒免疫反应的概念。(C) 2011 Elsevier Ltd.版权所有。
Dendritic cells (DCs) have been identified as the most effective antigen-presenting cell (APC), much attention has been directed toward the use of DCs in vaccine strategies for the treatment of cancer or chronic virus infection. B7-H1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) and does not bind to other CD28 family members, it is expressed on resting and upregulated on activated B, T, myeloid, and dendritic cells (DCs). The overwhelming number of studies supports the role of B7-H1 as a negative regulator of T cell responses. RNA interference (RNAi) is a mechanism for sequence-specific posttranscriptional inhibition of gene expression via double stranded RNA molecules and it has recently been applied to mammalian cells with the use of small interfering RNAs (siRNAs). In the study, transfection of DCs with siRNA specific for B7-H1 gene resulted in the blockade of the expression of B7-H1 on DCs. The allostimulatory activity of DCs could be enhanced by silencing of B7-H1 on DCs. Blockade of B7-H1 on DCs inhibited the production of IFN-gamma and IL-10 but not IL-2 and IL-4 in mixed lymphocyte reaction (MLR). HBV specific peptide-pulsed DCs could break tolerance and trigger specific CTL responses, the level of HBsAg and HBV DNA in sera of HBV transgenic mice decreased, whereas blockade of B7-H1 on DCs augmented the effects. These data strongly support the concept that blockade of B7-H1 can enhance DC-mediated antiviral immune responses. (C) 2011 Elsevier Ltd. All rights reserved.