Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, United States.
Curr Opin Virol. 2013 Jun;3(3):371-6. doi: 10.1016/j.coviro.2013.05.017. Epub 2013 Jun 7.
Memory T cells generated from acute infection or vaccination have the potential to provide the host with life-long immunity against re-infection. Protection by memory T cells is achieved through their acquired ability to persist at anatomical sites of the primary infection as well as maintaining a heightened ability to recall effector functions. The maintenance of CD8 and CD4 T cell function in a state of readiness is key to life-long immunity and manifest through changes in transcriptional regulation. Yet, the ability to identify poised transcriptional programs at the maintenance stage of the response is lacking from most transcriptional profiling studies of memory T cells. Epigenetic profiling allows for the assessment of transcriptionally poised (promoters that are readily accessible for transcription) states of antigen-specific T cells without manipulation of the activation state of the cell. Here we review recent studies that have examined epigenetic programs of effector and memory T cell subsets. These reports demonstrate that acquisition of epigenetic programs during memory T cell differentiation to acute and chronic infections is coupled to, and potentially regulate, the cell's recall response. We discuss the usefulness of epigenetic profiling in characterizing T cell differentiation state and function for preclinical evaluation of vaccines and the current methodologies for single locus versus genome-wide epigenetic profiling.
从急性感染或疫苗接种中产生的记忆 T 细胞有可能为宿主提供终身免受再次感染的免疫力。记忆 T 细胞的保护作用是通过其在初次感染的解剖部位持续存在的获得性能力以及维持高度回忆效应功能的能力来实现的。保持 CD8 和 CD4 T 细胞功能的预备状态是终身免疫的关键,表现在转录调节的变化上。然而,在大多数记忆 T 细胞的转录谱研究中,缺乏在反应维持阶段识别潜在转录程序的能力。表观遗传谱分析允许在不操纵细胞激活状态的情况下,评估抗原特异性 T 细胞的转录预备(可随时用于转录的启动子)状态。在这里,我们回顾了最近研究急性和慢性感染中效应和记忆 T 细胞亚群的表观遗传程序的研究。这些报告表明,在记忆 T 细胞分化为急性和慢性感染的过程中获得表观遗传程序与细胞的回忆反应相关联,并可能对其进行调节。我们讨论了表观遗传谱分析在描述 T 细胞分化状态和功能方面的有用性,用于疫苗的临床前评估,以及当前用于单基因座与全基因组表观遗传谱分析的方法。