Ciesek S, Liermann H, Hadem J, Greten T, Tillmann H L, Cornberg M, Aslan N, Manns M P, Wedemeyer H
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
J Viral Hepat. 2008 Mar;15(3):200-11. doi: 10.1111/j.1365-2893.2007.00930.x.
Dendritic cells (DCs) play a central role in antiviral immunity. Conflicting data on DC function have been reported for hepatitis C virus (HCV) infection. In addition to antigen presentation and cytokine secretion, a subset of human DCs displays direct cytotoxic activity. It has been suggested that measles virus and human immunodeficiency virus (HIV) may enhance cytotoxicity of DCs potentially leading to apoptosis of activated T cells and subsequent down-regulation of antiviral immune responses. We demonstrate that CD1c-positive myeloid DCs, but not BDCA-4-positive plasmacytoid DCs, are able to kill different target cells mainly via tumour necrosis factor-related apoptosis-inducing ligand. The ability of CD1c+ DCs to lyze target cells was found to be completely impaired in patients with chronic hepatitis C (10 chronic HCV patients vs 10 healthy controls; P < 0.001) but not in patients with primary biliary cirrhosis. Successful antiviral therapy of chronic hepatitis C rescued the cytotoxicity of DCs. Myeloid DCs of HCV patients and healthy controls had a similar phenotype and endocytotic activity, however, the frequency of mDCs in the peripheral blood was lower (P = 0.004) and the allostimulatory function was weaker (P < 0.001) in chronic hepatitis C. Thus, in contrast to HIV and measles virus studies on monocyte-derived DCs, freshly isolated myeloid DCs of patients with hepatitis C do not show an increased but a completely abolished cytotoxic activity. The impaired DC cytotoxicity could represent a novel mechanism for the increased prevalence of autoimmunity in HCV infection.
树突状细胞（DCs）在抗病毒免疫中发挥核心作用。关于丙型肝炎病毒（HCV）感染，已有关于DC功能的相互矛盾的数据报道。除了抗原呈递和细胞因子分泌外，一部分人类DC还表现出直接的细胞毒性活性。有人提出麻疹病毒和人类免疫缺陷病毒（HIV）可能增强DC的细胞毒性，这可能导致活化T细胞凋亡，进而下调抗病毒免疫反应。我们证明，CD1c阳性髓样DC而非BDCA - 4阳性浆细胞样DC能够主要通过肿瘤坏死因子相关凋亡诱导配体杀死不同的靶细胞。在慢性丙型肝炎患者中（10例慢性HCV患者与10例健康对照；P < 0.001），发现CD1c + DC裂解靶细胞的能力完全受损，但原发性胆汁性肝硬化患者未出现这种情况。慢性丙型肝炎的成功抗病毒治疗挽救了DC的细胞毒性。HCV患者和健康对照的髓样DC具有相似的表型和内吞活性，然而，慢性丙型肝炎患者外周血中mDC的频率较低（P = 0.004），共刺激功能较弱（P < 0.001）。因此，与关于HIV和麻疹病毒对单核细胞衍生DC的研究不同，丙型肝炎患者新鲜分离的髓样DC并未表现出细胞毒性活性增加，而是完全丧失。DC细胞毒性受损可能是HCV感染中自身免疫患病率增加的一种新机制。
