Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland.
Viruses. 2020 Jul 25;12(8):799. doi: 10.3390/v12080799.
The long-term consequences of T cell responses' impairment in chronic HCV infection are not entirely characterized, although they may be essential in the context of the clinical course of infection, re-infection, treatment-mediated viral clearance and vaccine design. Furthermore, it is unclear whether a complete reinvigoration of HCV-specific T cell response may be feasible. In most studies, attempting to reverse the effects of compromised immune response quality by specific blockades of negative immune regulators, a restoration of functional competence of HCV-specific T cells was shown. This implies that HCV-induced immune dysfunction may be reversible. The advent of highly successful, direct-acting antiviral treatment (DAA) for chronic HCV infection instigated investigation whether the treatment-driven elimination of viral antigens restores T cell function. Most of studies demonstrated that DAA treatment may result in at least partial restoration of T cell immune function. They also suggest that a complete restoration comparable to that seen after spontaneous viral clearance may not be attained, pointing out that long-term antigenic stimulation imprints an irreversible change on the T cell compartment. Understanding the mechanisms of HCV-induced immune dysfunction and barriers to immune restoration following viral clearance is of utmost importance to diminish the possible long-term consequences of chronic HCV infection.
慢性 HCV 感染中 T 细胞反应受损的长期后果尚未完全明确，尽管它们在感染的临床过程、再感染、治疗介导的病毒清除和疫苗设计的背景下可能是至关重要的。此外，尚不清楚是否可以完全恢复 HCV 特异性 T 细胞反应。在大多数研究中，通过特异性阻断负性免疫调节剂来试图逆转免疫反应质量受损的影响，显示 HCV 特异性 T 细胞的功能能力得到恢复。这意味着 HCV 诱导的免疫功能障碍可能是可逆的。直接作用抗病毒治疗（DAA）对慢性 HCV 感染的高度成功应用促使人们研究治疗驱动的病毒抗原消除是否恢复 T 细胞功能。大多数研究表明，DAA 治疗可能导致 T 细胞免疫功能至少部分恢复。它们还表明，可能无法达到与自发病毒清除后观察到的完全恢复相当的程度，指出长期的抗原刺激对 T 细胞区室造成不可逆转的改变。了解 HCV 诱导的免疫功能障碍的机制以及清除病毒后免疫恢复的障碍对于减少慢性 HCV 感染的可能长期后果至关重要。
