Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species.
Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species.
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DOI：
10.1002/hep.24700
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发表时间：
2012-02
期刊：
影响因子：
13.5
通讯作者：
Hahn, Young S.
中科院分区：
文献类型：
--
作者：
Tacke, Robert S.;Lee, Hai-Chon;Goh, Celeste;Courtney, Jeremy;Polyak, Stephen J.;Rosen, Hugo R.;Hahn, Young S.
据报道，慢性丙型肝炎病毒（HCV）患者的t细胞反应受损与HCV持续感染的建立有关。然而，hcv介导的t细胞功能障碍的机制尚未明确。髓源性抑制细胞（MDSCs）在抑制t细胞反应中起关键作用。在这项研究中，我们检测了HCV感染后人外周血单个核细胞（PBMCs）中MDSCs的积累。我们发现CD33+单核细胞与HCV感染的肝细胞或与HCV核心蛋白共培养可抑制自体t细胞反应。HCV核心处理的CD33+细胞表现出CD14+CD11b+/lowHLADR−/低表型，p47phox的表达上调，p47phox是NOX2复合物的一个组成部分，对活性氧（ROS）的产生至关重要。相反，免疫抑制因子精氨酸酶-1和诱导型一氧化氮合酶（iNOS）没有上调。重要的是，用ROS灭活剂治疗逆转了hcv诱导的MDSCs的t细胞抑制功能。最后，慢性HCV患者的PBMCs在HCV核心治疗后反映CD33+细胞，CD14+CD11b+HLADR−/低，并上调p47phox的表达。这些结果表明，HCV促进CD33+ MDSC的积累，导致ros介导的t细胞反应性抑制。因此，在HCV感染期间，MDSCs的积累可能促进和维持HCV持续感染。
Impaired T-cell responses in chronic hepatitis C virus (HCV) patients have been reported to be associated with the establishment of HCV persistent infection. However, the mechanism for HCV-mediated T-cell dysfunction is yet to be defined. Myeloid-derived suppressor cells (MDSCs) play a pivotal role in suppressing T-cell responses. In this study we examined the accumulation of MDSCs in human peripheral blood mononuclear cells (PBMCs) following HCV infection. We found that CD33+ mononuclear cells cocultured with HCV-infected hepatocytes, or with HCV core protein, suppress autologous T-cell responses. HCV core-treated CD33+ cells exhibit a CD14+CD11b+/lowHLADR−/low phenotype with up-regulated expression of p47phox, a component of the NOX2 complex critical for reactive oxygen species (ROS) production. In contrast, immunosuppressive factors, arginase-1 and inducible nitric oxide synthase (iNOS), were not up-regulated. Importantly, treatment with an inactivator of ROS reversed the T-cell suppressive function of HCV-induced MDSCs. Lastly, PBMCs of chronic HCV patients mirror CD33+ cells following treatment with HCV core where CD33+ cells are CD14+CD11b+HLADR−/low, and up-regulate the expression of p47phox. These results suggest that HCV promotes the accumulation of CD33+ MDSC, resulting in ROS-mediated suppression of T-cell responsiveness. Thus, the accumulation of MDSCs during HCV infection may facilitate and maintain HCV persistent infection.
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DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
5.4
作者：
Kanda, T;Basu, A;Ray, RB
通讯作者：
Ray, RB
影响因子：
4.8
作者：
Tacke, Robert S.;Tosello-Trampont, Annie;Hahn, Young S.
通讯作者：
Hahn, Young S.
影响因子：
15.9
作者：
Gelderman, Kyra A.;Hultqvist, Malin;Holmdahl, Rikard
通讯作者：
Holmdahl, Rikard
影响因子：
25.7
作者：
KANTO, T;HAYASHI, N;KAMADA, T
通讯作者：
KAMADA, T