Defining 'T cell exhaustion'
Defining 'T cell exhaustion'
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DOI：
10.1038/s41577-019-0221-9
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发表时间：
2019-11-01
影响因子：
100.3
通讯作者：
Zehn, Dietmar
中科院分区：
文献类型：
--
作者：
Blank, Christian U.;Haining, W. Nicholas;Zehn, Dietmar
T细胞衰竭‘是一个宽泛的术语，用来描述T细胞对慢性抗原刺激的反应，最初是在慢性病毒感染的背景下，但最近是对肿瘤的反应。了解衰竭的特征和途径对于检查点阻断和过继T细胞转移疗法的成功具有至关重要的意义。在这篇观点文章中，该领域的18位专家告诉我们疲惫对他们意味着什么，从完全缺乏效应器功能到预防免疫病理的功能改变，以及癌症和慢性感染之间的潜在差异。他们的反应突出了终末分化的耗竭T细胞TCF1(-)和从中衍生出的自我更新的TCF1(+)群体之间的二分性。一些人认为这些TCF1(+)细胞具有类似于记忆T细胞群体的干细胞样特性，但目前发育关系尚不清楚。最近的研究也强调了转录调节因子TOX在驱动表观遗传强制耗竭方面的重要作用，但关键问题仍然是逆转表观耗竭计划的可能性，以及这可能如何影响T细胞群体的持久性。
'T cell exhaustion' is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumours. Understanding the features of and pathways to exhaustion has crucial implications for the success of checkpoint blockade and adoptive T cell transfer therapies. In this Viewpoint article, 18 experts in the field tell us what exhaustion means to them, ranging from complete lack of effector function to altered functionality to prevent immunopathology, with potential differences between cancer and chronic infection. Their responses highlight the dichotomy between terminally differentiated exhausted T cells that are TCF1(-) and the self-renewing TCF1(+) population from which they derive. These TCF1(+) cells are considered by some to have stem cell-like properties akin to memory T cell populations, but the developmental relationships are unclear at present. Recent studies have also highlighted an important role for the transcriptional regulator TOX in driving the epigenetic enforcement of exhaustion, but key questions remain about the potential to reverse the epigenetic programme of exhaustion and how this might affect the persistence of T cell populations.