黏膜相关恒定T细胞在抗结核分枝杆菌免疫中的作用  

Role of MAIT cells in immunity against Mycobacterium tuberculosis

作　　者：曹志红[1] 程小星[1] Cao Zhihong;Cheng Xiaoxing(Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment,Senior Department of Tuberculosis,the Eighth Medical Center of PLA General Hospital,Beijing 100091,China)

机构地区：[1]解放军总医院第八医学中心结核病医学部研究所军队结核病防控重点实验室/结核病诊疗新技术北京市重点实验室,北京100091

出　　处：《中华结核和呼吸杂志》2023年第5期511-516,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金(82072233);解放军总医院第八医学中心课题(2021MS012)。

摘　　要：黏膜相关恒定T细胞(MAIT细胞)是一类固有免疫样T细胞,在人体内分布广泛。感染过程中,微生物合成的维生素B代谢物等抗原被主要组织相容性复合物样分子1(MR1)提呈给MAIT细胞,MAIT细胞活化后通过释放细胞因子和细胞毒性分子而发挥抗菌、抗病毒、抗癌和组织修复作用。动物和体外研究发现活动性结核病患者外周血中MAIT细胞数量减少,而且呈现功能耗竭表型,MAIT细胞被结核分枝杆菌抗原激活后通过炎性细胞因子如肿瘤坏死因子α、γ干扰素和细胞毒性分子如颗粒酶B(granzyme B)来发挥抗结核作用,这一作用依赖于MR1,同时依赖于细胞因子的调控。此外,MAIT细胞还可以作为天然性免疫和获得性免疫之间的桥梁,启动常规T细胞应答。目前对靶向MAIT细胞的疫苗和治疗药物也进行了相关实验研究,在结核病预防和控制方面表现出巨大潜力。本文对MAIT细胞的发现及分群、发育和激活、在抗结核分枝杆菌感染中的作用以及在结核病预防和治疗中的应用进行综述,以期为结核病预防和治疗提供新的免疫学靶点。Mucosal-associated invariant T cells(MAIT cells)are a class of innate immune-like T cells that are widely distributed in the human body.During infection,antigens such as vitamin B metabolites synthesized by microorganisms are presented to MAIT cells by MR1(major histocompatibility complex classⅠ-like molecule),and MAIT cells are activated and exert antibacterial,antiviral,anticancer and tissue repair effects by releasing cytokines and cytotoxic molecules.Animal and in vitro studies have shown that the number of MAIT cells in the peripheral blood of patients with active tuberculosis is reduced and the cells exhibit a functional exhaustion phenotype.MAIT cells are activated by Mycobacterium tuberculosis antigens and produce inflammatory cytokines such as TNF-α,IFN-γand cytotoxic molecules such as granzyme B to exert anti-tuberculosis effects that are MR1-dependent and cytokine-dependent.In addition,MAIT cells can also act as a bridge between innate and acquired immunity by initiating a conventional T-cell response.Currently,there are also relevant experimental studies on vaccines and drugs targeting MAIT cells,which show great potential in the prevention and control of tuberculosis.In this article,we will review the discovery and grouping,development and activation of MAIT cells,their role in Mycobacterium tuberculosis infection,and their application in tuberculosis prevention and treatment,in order to provide new immunological targets for tuberculosis prevention and treatment.

关 键 词：活动性结核病 结核病预防 固有免疫 主要组织相容性复合物 感染过程 细胞毒性 颗粒酶B 细胞因子 

分 类 号：R392[医药卫生—免疫学]