Racanelli Vito, Manigold Tobias
Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico-11, Piazza G. Cesare, Bari, Italy.
Clin Immunol. 2007 Jul;124(1):5-12. doi: 10.1016/j.clim.2007.04.009. Epub 2007 May 31.
T cell-mediated protection against HCV depends on constantly activated effector CD8(+)T cells that control emergence, spread and expansion of the virus. Why these cells fail to contain HCV replication in 70-80% of the individuals who develop persistent viremia is not clear. Although many reviews have focused on HCV's ability to interfere with the process of antigen presentation by dendritic cells (DC), only few have discussed the mechanisms whereby HCV-derived antigens become available for presentation to naive CD8(+)T cells. The importance of these mechanisms has been recently brought to light by new insight into DC biology, antigen processing, HCV replication and the immune system's functional anatomy. This review explores the different immunological scenarios in which CD8(+)T cell responses against HCV may be initiated. It describes the critical factors limiting antigen sensing and capture by APC and antigen recognition by T cells, and discusses how these factors may favor chronicity of HCV infection. Despite the lack of critical detail and hard experimental proof, this review proposes a model whereby liver seclusion, unproductive infection of professional antigen presenting cells and lack of direct tissue damage hamper the launch of a virus-specific CD8(+)T cell response. The implications for vaccine development are also discussed.
T细胞介导的针对丙型肝炎病毒（HCV）的保护作用依赖于持续活化的效应性CD8(+)T细胞，这些细胞控制着病毒的出现、传播和扩散。在70%-80%发生持续性病毒血症的个体中，这些细胞为何未能抑制HCV复制尚不清楚。尽管许多综述聚焦于HCV干扰树突状细胞（DC）抗原呈递过程的能力，但只有少数综述讨论了HCV衍生抗原可供呈递给初始CD8(+)T细胞的机制。最近，对DC生物学、抗原加工、HCV复制及免疫系统功能解剖的新认识揭示了这些机制的重要性。本综述探讨了可能启动针对HCV的CD8(+)T细胞应答的不同免疫情况。它描述了限制抗原呈递细胞（APC）感知和捕获抗原以及T细胞识别抗原的关键因素，并讨论了这些因素如何促进HCV感染的慢性化。尽管缺乏关键细节和确凿的实验证据，但本综述提出了一个模型，即肝脏隔离、专业抗原呈递细胞的非生产性感染以及缺乏直接组织损伤阻碍了病毒特异性CD8(+)T细胞应答的启动。文中还讨论了对疫苗开发的影响。
