Major histocompatibility complex class‐I presentation impaired in transgenic mice expressing hepatitis C virus structural proteins during dendritic cell maturation
Major histocompatibility complex class‐I presentation impaired in transgenic mice expressing hepatitis C virus structural proteins during dendritic cell maturation
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在树突状细胞成熟过程中表达丙型肝炎病毒结构蛋白的转基因小鼠中主要组织相容性复合体 I 类表达受损
DOI：
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发表时间：
2004
影响因子：
12.7
通讯作者：
M. Kohara
中科院分区：
文献类型：
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作者：
Y. Hiasa;Hidemi Takahashi;Masumi Shimizu;H. Nuriya;K. Tsukiyama;Takeshi Tanaka;N. Horiike;M. Onji;M. Kohara
丙型肝炎病毒（HCV）感染往往是持续性的，但其机制和发病机制仍不清楚。HCV逃避全身免疫监视的一种机制可能是通过受损的树突状细胞（DC），这是最有效的抗原呈递细胞类型。我们研究了HCV是否会导致成熟过程中的DC免疫抑制。我们从携带表达HCV结构蛋白（核苷酸294-3435）的HCV cDNA的转基因小鼠的两个创始人谱系的骨髓中分离出未成熟的DC，并研究了DC功能如何被HCV表达修饰。我们的数据显示，表达HCV结构蛋白的DC刺激T细胞的能力显著受损。此外，主要组织相容性复合体（MHC）I类分子的表面表达在感染的DC上显著受损，特别是在H-2D方面。DC成熟过程中H-2D向细胞表面的转运受到HCV表达的抑制。然而，表达HCV的DC产生的H-2D分子的总量没有受损。结果提示，HCV感染DC后，DC的免疫功能下降，这可能与HCV持续感染的机制有关。医学病毒学杂志74：253-261，2004.© 2004 Wiley利斯公司
Hepatitis C virus (HCV) infection is often persistent, but its mechanism and pathogenesis remain unclear. One mechanism through which HCV escapes systemic immunosurveillance might be via impaired dendritic cells (DCs), which are the most potent type of antigen‐presenting cells. We examined whether HCV causes immunosuppression in DCs during maturation. We isolated immature DCs from the bone marrow of two founder lineages of transgenic mice harboring HCV cDNA expressing HCV structural proteins (nucleotides 294–3435), and studied how DC function is modified by HCV expression. Our data showed that the capacity of DCs expressing HCV structural proteins to stimulate T‐cells was significantly impaired. Moreover, the surface expression of major histocompatibility complex (MHC) class‐I molecules was significantly impaired on infected DC, especially with respect to H‐2D. The transportation of H‐2D to the cell surface during DC maturation was inhibited by HCV expression. However, the total amount of H‐2D molecules produced by DC expressing HCV was not impaired. These results indicated that the immune response of DC infected with HCV is diminished and might be associated with the mechanism of persistent HCV infection. J. Med. Virol. 74:253–261, 2004. © 2004 Wiley‐Liss, Inc.
影响因子：
20.3
作者：
Longman, RS;Talal, AH;Rice, CM
通讯作者：
Rice, CM
影响因子：
20.3
作者：
Auffermann-Gratzinger, S;Keeffe, EB;Levy, S
通讯作者：
Levy, S
影响因子：
32.4
作者：
Cooper, S;Erickson, AL;Walker, CM
通讯作者：
Walker, CM