Collins Matthew H, Henderson Andrew J
aDepartment of Medicine bSection of Infectious Diseases, Boston University Medical Center, Boston, Massachusetts, USA.
Curr Opin HIV AIDS. 2014 Sep;9(5):459-63. doi: 10.1097/COH.0000000000000091.
This review highlights the control of transcriptional networks, including induction of inhibitory receptors, by T cell-specific transcription factors in exhausted T cells that accumulate in chronic viral infections including HIV.
Transcriptional profiling has established distinct molecular phenotypes for exhausted CD4 and CD8 T cells in chronic viral infection models. There exists a subset of transcription factors associated with exhaustion, notably Blimp-1, basic leucine zipper transcription factor, ATF-like and Helios. Epigenetic phenomena are likely important in regulating gene expression networks during exhaustion as illustrated by programmed death 1 promoter methylation patterns.
Following chronic viral infections, CD4 and CD8 T cells defined functionally and phenotypically as exhausted have distinct transcriptional profiles. These studies have identified a core set of transcription factors that have been implicated in promoting exhaustion. However, no single factor appears to be an exhaustion determining factor, suggesting that T cell exhaustion reflects a combinatorial mechanism with multiple transcription factors interacting to influence the development of functionally exhausted T cells as well as different T effector populations.
本综述重点介绍了转录网络的调控，包括在慢性病毒感染（如HIV感染）中积累的耗竭T细胞中，T细胞特异性转录因子对抑制性受体的诱导作用。
转录谱分析已确定了慢性病毒感染模型中耗竭的CD4和CD8 T细胞的不同分子表型。存在与耗竭相关的一类转录因子，尤其是B淋巴细胞诱导成熟蛋白-1、碱性亮氨酸拉链转录因子、ATF样蛋白和Helios。如程序性死亡1启动子甲基化模式所示，表观遗传现象可能在耗竭过程中调节基因表达网络方面发挥重要作用。
在慢性病毒感染后，功能和表型上定义为耗竭的CD4和CD8 T细胞具有不同的转录谱。这些研究已经确定了一组核心转录因子，它们与促进耗竭有关。然而，似乎没有单一因素是决定耗竭的因素，这表明T细胞耗竭反映了一种组合机制，其中多个转录因子相互作用，影响功能耗竭T细胞以及不同T效应细胞群体的发育。
