{"title":"T Cell Exhaustion.","authors":"Andrew Baessler, Dario A A Vignali","doi":"10.1146/annurev-immunol-090222-110914","DOIUrl":null,"url":null,"abstract":"<p><p>T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.</p>","PeriodicalId":8271,"journal":{"name":"Annual review of immunology","volume":null,"pages":null},"PeriodicalIF":26.9000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-immunol-090222-110914","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/14 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.
T 细胞反应必须保持平衡,以确保对恶性转化和一系列病原体提供充分保护,同时限制对健康细胞的损害并防止自身免疫。T 细胞衰竭是一种调节机制,可限制长期受抗原刺激的 T 细胞的活性和效应功能。衰竭的 T 细胞增殖潜力差;抑制性受体表达高;转录组、表观基因组和新陈代谢改变;最重要的是,效应功能降低。虽然衰竭有助于抑制自身免疫性疾病中异常 T 细胞造成的损害,但它也限制了细胞应对持续感染和癌症的能力,从而导致疾病进展。在此,我们回顾了 T 细胞衰竭的过程,详细介绍了其关键特征和驱动因素,并强调了我们目前对其背后的转录和表观遗传编程的理解。我们还将讨论如何以衰竭为靶点,增强癌症中 T 细胞的功能。免疫学年刊》(Annual Review of Immunology)第42卷的最终在线出版日期预计为2024年4月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
期刊介绍:
The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.