Evergrande Center for Immunologic Diseases and Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Trends Immunol. 2017 Aug;38(8):567-576. doi: 10.1016/j.it.2017.05.008. Epub 2017 Jun 26.
Chronic viral infections and cancer often lead to the emergence of dysfunctional or 'exhausted' CD8 T cells, and the restoration of their functions is currently the focus of therapeutic interventions. In this review, we detail recent advances in the annotation of the gene modules and the epigenetic landscape associated with T-cell dysfunction. Together with analysis of single-cell transcriptomes, these findings have enabled a deeper and more precise understanding of the transcriptional mechanisms that induce and maintain the dysfunctional state and highlight the heterogeneity of CD8 T-cell phenotypes present in chronically inflamed tissue. We discuss the relevance of these findings for understanding the transcriptional and spatial regulation of dysfunctional T cells and for the design of therapeutics.
慢性病毒感染和癌症常导致功能失调或“耗竭”的 CD8 T 细胞的出现，而恢复其功能目前是治疗干预的重点。在这篇综述中，我们详细介绍了 T 细胞功能障碍相关基因模块和表观遗传景观注释的最新进展。结合单细胞转录组分析，这些发现使我们能够更深入、更精确地理解诱导和维持功能失调状态的转录机制，并突出了慢性炎症组织中存在的 CD8 T 细胞表型的异质性。我们讨论了这些发现对于理解功能失调 T 细胞的转录和空间调控以及治疗药物设计的相关性。
