Selective functional deficit in dendritic cell - T cell interaction is a crucial mechanism in chronic hepatitis B virus infection
Selective functional deficit in dendritic cell - T cell interaction is a crucial mechanism in chronic hepatitis B virus infection
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DOI：
10.1111/j.1365-2893.2004.00497.x
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发表时间：
2004-05-01
影响因子：
2.5
通讯作者：
Wen, YM
中科院分区：
文献类型：
--
作者：
Zheng, BJ;Zhou, J;Wen, YM
长期以来，特异性T细胞免疫缺陷一直被认为是持续性B型肝炎病毒（HBV）感染的中心机制。最近的HBV转基因小鼠研究表明。然而，树突状细胞（DC）功能缺陷是T细胞功能障碍的潜在原因。通过研究75名受试者来确定单核细胞来源的DC的功能，这些受试者包括具有低或高HBV载量的慢性B肝炎患者：从先前的急性HBV感染中完全恢复的抗B表面抗原（抗-HBs）抗体阳性个体;接受过B肝炎疫苗接种且抗-HBs阳性的健康供体;以及对HBV或疫苗个体免疫学上未处理的个体。在慢性HBV感染患者中，特别是在病毒复制活跃的患者中，单核细胞来源的DC和T细胞之间的相互作用受损。功能障碍包括：（i）DC不能响应于肝炎B表面抗原（HBsAg）而增加人白细胞抗原（HLA-II）、B7表达和白细胞介素-12分泌，（ii）对HBsAg的T细胞增殖应答的诱导缺陷，（iii）不能活化T细胞以产生细胞因子和（iv）抗原特异性细胞毒性T淋巴细胞（CTL）的诱导缺陷。在体外治疗的DC与肿瘤坏死因子-α改善HLA-II和B7的表达，以及Th细胞和CTL反应。结论：DC-T细胞相互作用缺陷可能是慢性HBV感染中特异性T细胞免疫缺陷的原因。旨在恢复DC功能的免疫疗法可以为有效管理持续性HBV感染提供新的机会。
A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested. however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load: antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection: healthy donors who had received hepatitis B vaccination and were anti-HBs positive: and immunologically naive to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.