Rehermann Barbara
Immunology Section, Liver Diseases Branch, NIDDK, National Institutes of Health, DHHS, Bethesda, Maryland 20892, USA.
Semin Liver Dis. 2007 May;27(2):152-60. doi: 10.1055/s-2007-979468.
Chronic hepatitis B and C cause significant morbidity and mortality worldwide. Antiviral therapy suppresses but does not eliminate chronic hepatitis B virus (HBV) infection, and it is effective in only half of all hepatitis C virus (HCV)-infected patients. Because adaptive immune responses are associated with spontaneous resolution of acute HBV and HCV infection, therapeutic enhancement of immune responses has been proposed as alternative or supplementary therapy for chronic infection. However, all efforts have been hampered by poor proliferation and effector functions of HBV- and HCV-specific CD4 and CD8 T cells, which are thought to be due to T cell exhaustion, high antigenic load, and viral escape. Recent studies revealed that endogenous factors, such as regulatory T cells, immunosuppressive cytokines, and inhibitory receptors, also contribute to the impairment of virus-specific T cell responses in chronic infection, perhaps reflecting the host's attempt to protect itself against immune-mediated pathology. These endogenous mechanisms and potential avenues to revert them are the subject of this review.
慢性乙型肝炎和丙型肝炎在全球范围内导致了严重的发病率和死亡率。抗病毒治疗可抑制但不能消除慢性乙型肝炎病毒（HBV）感染，并且仅对一半的丙型肝炎病毒（HCV）感染患者有效。由于适应性免疫反应与急性HBV和HCV感染的自发缓解相关，因此已提出增强免疫反应作为慢性感染的替代或补充治疗方法。然而，所有努力都因HBV和HCV特异性CD4和CD8 T细胞的增殖和效应功能不佳而受阻，这被认为是由于T细胞耗竭、高抗原负荷和病毒逃逸所致。最近的研究表明，内源性因素，如调节性T细胞、免疫抑制细胞因子和抑制性受体，也导致慢性感染中病毒特异性T细胞反应受损，这可能反映了宿主保护自身免受免疫介导病理的尝试。这些内源性机制及其逆转的潜在途径是本综述的主题。
