van der Molen Renate G, Sprengers Dave, Biesta Paula J, Kusters Johannes G, Janssen Harry L A
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Hepatology. 2006 Oct;44(4):907-14. doi: 10.1002/hep.21340.
In patients with chronic hepatitis B virus (HBV), 2 predominant precursor dendritic cell (DC) subtypes, the myeloid dendritic cell (mDC) and the plasmacytoid dendritic cell (pDC), were recently found to be functionally impaired. HBV DNA was found to be present in the DC subtypes, but no viral replication could be detected. The question remains whether simply the presence of the virus and viral proteins causes this dysfunction of DCs. To address this issue, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the number and functionality of circulating DCs was studied during 6 months of treatment. Treatment resulted in a mean 5 log(10) decrease in the viral load and normalization of alanine aminotransferase within 3 months. The number of mDCs, but not of pDCs, increased significantly over 6 months of treatment to a level comparable to that of uninfected healthy controls. The allostimulatory capacity of isolated and in vitro matured mDCs increased significantly after 3 months of treatment. Accordingly, mDCs exhibited an increased capacity to produce tumor necrosis factor alpha and interleukin-12 after 3-6 months of treatment. There was no change in interferon alpha production by pDCs during treatment. In conclusion, adefovir treatment results in an improvement in the number and functionality of mDCs, but not of pDCs. Our findings provide clues for the reasons why current antiviral therapy does not lead to consistently sustained viral eradication.
在慢性乙型肝炎病毒（HBV）患者中，最近发现两种主要的前体树突状细胞（DC）亚型，即髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC），功能受损。在DC亚型中发现了HBV DNA，但未检测到病毒复制。问题仍然是，仅仅病毒和病毒蛋白的存在是否会导致DC功能障碍。为了解决这个问题，在治疗的6个月期间，研究了用核苷酸类似物阿德福韦酯治疗导致病毒载量降低对循环DC数量和功能的影响。治疗导致病毒载量平均降低5个对数（10），并在3个月内使丙氨酸转氨酶恢复正常。在治疗的6个月期间，mDC的数量显著增加，但pDC的数量没有增加，增加后的水平与未感染的健康对照相当。治疗3个月后，分离并在体外成熟的mDC的共刺激能力显著增加。因此，治疗3至6个月后，mDC产生肿瘤坏死因子α和白细胞介素-12的能力增强。治疗期间pDC产生α干扰素的能力没有变化。总之，阿德福韦治疗可改善mDC的数量和功能，但不能改善pDC的数量和功能。我们的研究结果为当前抗病毒治疗不能始终如一地持续清除病毒的原因提供了线索。
