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理解黏膜相关恒定 T 细胞在 HIV 感染非人类灵长类动物模型中的作用。

Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection.

机构信息

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.

Department of Infectious Diseases, Melbourne Sexual Health Centre, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia.

出版信息

Front Immunol. 2020 Aug 18;11:2038. doi: 10.3389/fimmu.2020.02038. eCollection 2020.

Abstract

Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Non-human primates (NHPs) are a valuable, well-described animal model for HIV infection in humans. NHPs also maintain MAIT cell frequencies more comparable to humans, compared to other common animal models, and provide a unique opportunity to study MAIT cells in the circulation and mucosal tissues in a longitudinal manner. Only recently, however, have NHP MAIT cells been thoroughly characterized using macaque-specific MR1 tetramer reagents. Here we review the similarities and differences between MAIT cells in humans and NHPs as well as the impact of SIV/SHIV infection on MAIT cells and the potential implications for future research.

摘要

慢性 HIV 感染会导致全身免疫激活和失调,从而损害包括 MAIT 细胞在内的大多数 T 细胞亚群。多项人类队列研究表明,在 HIV 感染期间,MAIT 细胞在外周血和淋巴组织中被选择性耗竭,在抑制性抗逆转录病毒治疗期间不能完全恢复。由于 MAIT 细胞在粘膜防御多种病原体方面发挥着重要作用,因此在接受 ART 治疗的人群中完全重建 MAIT 细胞区室可能会改善对合并感染的免疫力。非人类灵长类动物(NHP)是一种有价值的、描述完善的人类 HIV 感染动物模型。与其他常见的动物模型相比,NHP 也能更好地维持 MAIT 细胞频率,并且为以纵向方式在循环和粘膜组织中研究 MAIT 细胞提供了独特的机会。然而,直到最近,才使用猴特异性 MR1 四聚体试剂对 NHP MAIT 细胞进行了彻底的表征。在这里,我们综述了人类和 NHP 中的 MAIT 细胞之间的相似性和差异,以及 SIV/SHIV 感染对 MAIT 细胞的影响,以及对未来研究的潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a562/7461791/d1c9a12b94c7/fimmu-11-02038-g001.jpg

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