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CD8+ T cell exhaustion.
Seminars in Immunopathology ( IF 7.9 ) Pub Date : 2019-04-15 , DOI: 10.1007/s00281-019-00744-5
Makoto Kurachi 1
Affiliation  

CD8+ T cells are important for the protective immunity against intracellular pathogens and tumor. In the case of chronic infection or cancer, CD8+ T cells are exposed to persistent antigen and/or inflammatory signals. This excessive amount of signals often leads CD8+ T cells to gradual deterioration of T cell function, a state called “exhaustion.” Exhausted T cells are characterized by progressive loss of effector functions (cytokine production and killing function), expression of multiple inhibitory receptors (such as PD-1 and LAG3), dysregulated metabolism, poor memory recall response, and homeostatic proliferation. These altered functions are closely related with altered transcriptional program and epigenetic landscape that clearly distinguish exhausted T cells from normal effector and memory T cells. T cell exhaustion is often associated with inefficient control of persisting infections and cancers, but re-invigoration of exhausted T cells with inhibitory receptor blockade can promote improved immunity and disease outcome. Accumulating evidences support the therapeutic potential of targeting exhausted T cells. However, exhausted T cells comprise heterogenous cell population with distinct responsiveness to intervention. Understanding molecular mechanism of T cell exhaustion is essential to establish rational immunotherapeutic interventions.

中文翻译:

CD8 + T细胞衰竭。

CD8 + T细胞对于抵抗细胞内病原体和肿瘤的保护性免疫非常重要。在慢性感染或癌症的情况下,CD8 + T细胞暴露于持久性抗原和/或炎症信号。这种过多的信号通常会导致CD8 +T细胞使T细胞功能逐渐退化,这种状态称为“精疲力竭”。精疲力竭的T细胞的特征是效应器功能(细胞因子的产生和杀伤功能)的逐步丧失,多种抑制性受体(如PD-1和LAG3)的表达,代谢失调,记忆力较差的记忆反应和体内稳态增殖。这些改变的功能与改变的转录程序和表观遗传环境密切相关,后者清楚地将疲惫的T细胞与正常效应细胞和记忆T细胞区分开来。T细胞衰竭通常与持续感染和癌症的无效控制有关,但是用抑制性受体阻滞使疲惫的T细胞重新活跃可以促进免疫力和疾病结局的改善。越来越多的证据支持靶向耗尽T细胞的治疗潜力。但是,精疲力竭的T细胞包含异种细胞群体,对干预具有独特的反应能力。了解T细胞衰竭的分子机制对于建立合理的免疫治疗干预至关重要。
更新日期:2019-04-15
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