Viral Vaccine Program, Seattle Biomedical Research Institute (Seattle Biomed), Seattle, WA 98109, USA.
Int J Biochem Cell Biol. 2012 Aug;44(8):1361-5. doi: 10.1016/j.biocel.2012.05.003. Epub 2012 May 14.
Cytotoxic CD8 T lymphocytes (CTLs) have an astonishing ability to eliminate pathogen-infected cells. However, if uncontrolled, these CTLs could cause devastating pathology to host tissues. CD8(+) effector T cells, therefore, interact with antigen-presenting cells and other immune cells, such as regulatory T cells (Tregs), to regulate further on-site expansion and differentiation of the effector cells. This ensures protection of the host with minimal bystander pathological consequences. During prolonged chronic infections CTLs, however, often lose effector function. Induction of multiple inhibitory pathways is emerging as a major regulator converting effector CTLs into exhausted CTLs during chronic viral infections such as HIV, HCV and HBV. The mechanisms involved in induction of exhaustion during chronic viral infections are the focus of this article. Blockade of inhibitory pathways could potentially restore functional capabilities to exhausted CTLs and represents a potential immune-based intervention in chronic viral infections.
细胞毒性 CD8 T 淋巴细胞（CTL）具有惊人的能力来清除病原体感染的细胞。然而，如果不受控制，这些 CTL 可能会对宿主组织造成毁灭性的病理损伤。因此，CD8(+)效应 T 细胞与抗原呈递细胞和其他免疫细胞（如调节性 T 细胞（Treg））相互作用，以调节效应细胞在现场的进一步扩增和分化。这确保了宿主的保护，同时最小化了旁观者病理后果。然而，在长期慢性感染中，CTL 通常会失去效应功能。在慢性病毒感染（如 HIV、HCV 和 HBV）期间，诱导多种抑制途径已成为将效应 CTL 转化为耗竭 CTL 的主要调节剂。本文重点介绍了慢性病毒感染中诱导耗竭的机制。抑制途径的阻断可能会潜在地恢复衰竭 CTL 的功能能力，并代表了慢性病毒感染中一种潜在的基于免疫的干预措施。
