PD-1 coinhibitory signals: the link between pathogenesis and protection.
PD-1 coinhibitory signals: the link between pathogenesis and protection.
复制标题
DOI：
10.1016/j.smim.2013.02.002
复制
发表时间：
2013-10-31
影响因子：
7.8
通讯作者：
Sékaly RP
中科院分区：
文献类型：
--
作者：
Kulpa DA;Lawani M;Cooper A;Peretz Y;Ahlers J;Sékaly RP
在大多数HIV-1感染个体中，适应性免疫应答驱动病毒逃逸，导致持续的病毒血症和缺乏免疫介导的控制。在慢性HIV感染期间，负调控分子如PD-1的表达提供了区分功能性记忆T细胞亚群和具有衰竭表型的T细胞频率的有用标志物。此外，基于细胞的病毒持久性测量等同于活化标志物和表达PD-1的CD 4 T细胞的频率。在造血和非造血细胞上发现PD-1及其配体PD-L1和PD-L2的高水平表达，其受慢性抗原刺激、1型和II型干扰素（IFN）和稳态细胞因子的调节。在HIV感染的受试者中，CD 4和CD 8 T细胞上的PD-1水平在联合抗逆转录病毒疗法（cART）后继续保持高水平。系统生物学方法已经开始阐明由CD 4和CD 8 T细胞亚群中的PD-1表达调节的信号转导途径，这些T细胞亚群通过慢性TCR活化和PD-1信号传导而变得功能障碍。在这篇综述中，我们总结了我们目前的理解与免疫衰竭相关的转录特征和信号转导途径，重点是最近在我们的实验室表征PD-1在T细胞功能障碍和HIV发病机制中的作用。我们还强调了阻断PD-1-PD-L1和其他免疫检查点的治疗潜力，以激活针对慢性病毒感染和癌症的有效细胞免疫应答。
In the majority of HIV-1 infected individuals, the adaptive immune response drives virus escape resulting in persistent viremia and a lack of immune-mediated control. The expression of negative regulatory molecules such as PD-1 during chronic HIV infection provides a useful marker to differentiate functional memory T cell subsets and the frequency of T cells with an exhausted phenotype. In addition, cell-based measurements of virus persistence equate with activation markers and the frequency of CD4 T cells expressing PD-1. High-level expression of PD-1 and its ligands PD-L1 and - L2 are found on hematopoietic and non-hematopoietic cells, which are regulated by chronic antigen stimulation, Type 1 and Type II interferons (IFNs), and homeostatic cytokines. In HIV infected subjects, PD-1 levels on CD4 and CD8 T cells continue to remain high following combination anti-retroviral therapy (cART). System biology approaches have begun to elucidate signal transduction pathways regulated by PD-1 expression in CD4 and CD8 T cell subsets that become dysfunctional through chronic TCR activation and PD-1 signaling. In this review, we summarize our current understanding of transcriptional signatures and signal transduction pathways associated with immune exhaustion with a focus on recent work in our laboratory characterizing the role of PD-1 in T cell dysfunction and HIV pathogenesis. We also highlight the therapeutic potential of blocking PD-1-PD-L1 and other immune checkpoints for activating potent cellular immune responses against chronic viral infections and cancer.
登录
查看更多内容
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
4.4
作者：
Fuller, MJ;Zajac, AJ
通讯作者：
Zajac, AJ
影响因子：
5.7
作者：
Che, Karlhans Fru;Shankar, Esaki Muthu;Larsson, Marie
通讯作者：
Larsson, Marie
影响因子：
64.8
作者：
Champagne, P;Ogg, GS;Pantaleo, G
通讯作者：
Pantaleo, G
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John