《生命科学》 2020, 32(4): 349-358

免疫检查点阻断在逆转慢性结核病T细胞耗竭中的应用

陈珍妍，胡志东，范小勇*

(复旦大学附属公共卫生临床中心，上海 201058)

摘　要：

摘　要：抗原特异性T 细胞是机体抗感染和抗肿瘤免疫应答的关键因素。持续的抗原刺激可能导致T细胞耗竭，其特征为效应性T 细胞应答能力变弱、细胞因子分泌能力降低、抑制性受体持续表达和转录状态改变等。现有研究表明，免疫检查点阻断可逆转肿瘤和HIV、HBV 等慢性感染过程中的T 细胞耗竭，但是其在逆转慢性结核病T 细胞耗竭中的作用尚不明确。该综述讨论了持续性结核菌感染诱导T细胞耗竭的发生机制，慢性结核菌感染中表达上调的抑制性受体CTLA-4、PD-1、TIM-3、LAG-3、KLRG1、2B4和BTLA的研究现状，预防和扭转T 细胞耗竭状态以增强结核菌控制的策略等。这些研究将对靶向T 细胞耗竭的结核病免疫治疗有重要提示。

Reversion of T-cell exhaustion in chronic tuberculosis infection by immune checkpoint blockade

CHEN Zhen-Yan， HU Zhi-Dong， FAN Xiao-Yong*

(Shanghai Public Health Clinical Center， Fudan University， Shanghai 201058， China)

Abstract:

Abstract: Antigen-specific T cells are crucial for the anti-infective and anti-tumor immunity. Persistent antigen stimulation usually results in the exhaustion of T cells， characterized by poor effector function， decreased cytokinesecretion ability， persistent expression of inhibitory receptors， and altered transcriptional status. It has been observed that immune checkpoint blockade can reverse T-cell exhaustion in tumors and chronic infection models such as HIV， HBV， and so on， but its role in reversing chronic tuberculosis (TB) T-cell exhaustion remains unclear. In this review， we discuss the mechanism of T-cell exhaustion induced by persistent TB infection; the research progress of up-regulated inhibitory receptors such as CTLA-4， PD-1， TIM-3， LAG-3， KLRG1， 2B4 and BTLA in chronic TB infection; as well as strategies for preventing and reversing exhaustion to favor Mycobacterium tuberculosis control. These could provide clues on designing immunotherapies targeting T-cell efficacy reinvigoration to protect patients infected with TB.