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Hepatitis B virus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape

机译:乙肝病毒诱导的单核细胞衍生树突状细胞缺陷导致体外T辅助1型应答受损:病毒免疫逃逸的机制

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摘要

Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from patients with chronic hepatitis B virus (HBV) infection are functionally impaired. In our present study MoDC from healthy subjects were propagated in vitro and inoculated with HBV particles to investigate the precise mechanisms that underly MoDC dysfunction. T-cell proliferation assays revealed an impaired allostimulatory capacity of HBV-inoculated MoDC (HBV-MoDC) as well as a lower potential of stimulating autologous T cells against a recall antigen in comparison to control-MoDC. Interleukin-2, tumour necrosis factor-α and interferon-γ production by T cells in proliferation assays with HBV-MoDC was significantly lower than with control-MoDC and correlated with lower IL-12 production in HBV-MoDC cultures. The presence of the nucleoside analogue lamivudine (3TC), an inhibitor of HBV replication, restored impaired allostimulatory function of HBV-MoDC and up-regulated major histocompatibility complex class II expression. These results show that HBV infection compromises the antigen-presenting function of MoDC with concomitant impairment of T helper cell type 1 responses. This may play an important role for viral immune escape leading to chronic HBV infection. However, 3TC treatment can overcome HBV-MoDC-related T-cell hyporeactivity and this underscores its important role in enhanced immune responses to HBV.
机译:树突状细胞(DC)是最有效的抗原呈递细胞,在诱导抗病毒免疫反应中起着核心作用。最近,我们发现慢性乙型肝炎病毒(HBV)感染患者的单核细胞衍生DC(MoDC)功能受损。在我们目前的研究中,健康受试者的MoDC在体外繁殖并接种HBV颗粒,以研究潜在的MoDC功能障碍的确切机制。 T细胞增殖试验显示,与对照MoDC相比,HBV接种的MoDC(HBV-MoDC)的同种异体刺激能力受损,刺激自体T细胞抵抗召回抗原的可能性也较低。在HBV-MoDC的增殖试验中,T细胞产生的白细胞介素2,肿瘤坏死因子-α和干扰素-γ的含量显着低于对照-MoDC,并且与HBV-MoDC培养物中IL-12的产生较低有关。核苷类似物拉米夫定(3TC)(一种HBV复制抑制剂)的存在可恢复HBV-MoDC的同种异体刺激功能受损,并上调主要的组织相容性复合物II类表达。这些结果表明,HBV感染损害了MoDC的抗原呈递功能,并伴有1型T辅助细胞应答的损害。这可能对导致慢性HBV感染的病毒免疫逃逸起重要作用。然而,3TC治疗可以克服HBV-MoDC相关的T细胞反应性低下,这突出了其在增强对HBV的免疫反应中的重要作用。

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