Department of Pathology and Committee on Immunology, and.
Institute for Genomics and Systems Biology and Department of Human Genetics, The University of Chicago, Chicago, IL 60637.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8559-64. doi: 10.1073/pnas.1401750111. Epub 2014 May 27.
Chronic viral infections incapacitate adaptive immune responses by "exhausting" virus-specific T cells, inducing their deletion and reducing productive T-cell memory. Viral infection rapidly induces death receptor CD95 (Fas) expression by dendritic cells (DCs), making them susceptible to elimination by the immune response. Lymphocytic choriomeningitis virus (LCMV) clone 13, which normally establishes a chronic infection, is rapidly cleared in C57Black6/J mice with conditional deletion of Fas in DCs. The immune response to LCMV is characterized by an extended survival of virus-specific effector T cells. Moreover, transfer of Fas-negative DCs from noninfected mice to preinfected animals results in either complete clearance of the virus or a significant reduction of viral titers. Thus, DC-specific Fas expression plays a role in regulation of antiviral responses and suggests a strategy for stimulation of T cells in chronically infected animals and humans to achieve the clearance of persistent viruses.
慢性病毒感染通过“耗尽”病毒特异性 T 细胞来使适应性免疫应答失能，导致其被删除并减少有效的 T 细胞记忆。病毒感染会迅速诱导树突状细胞 (DC) 表达死亡受体 CD95（Fas），使其易受免疫反应的清除。淋巴细胞性脉络丛脑膜炎病毒 (LCMV) 克隆 13 通常会导致慢性感染，但在 Fas 在 DC 中条件性缺失的 C57Black6/J 小鼠中会迅速被清除。对 LCMV 的免疫应答特征是病毒特异性效应 T 细胞的存活时间延长。此外，将来自未感染小鼠的 Fas 阴性 DC 转移到预先感染的动物中，会导致病毒完全清除或病毒滴度显著降低。因此，DC 特异性 Fas 表达在调节抗病毒反应中起作用，并为刺激慢性感染动物和人类的 T 细胞以清除持续性病毒提供了一种策略。
