MAIT Cell Loss and Reconstitution in HIV-1 Disease
MAIT Cell Loss and Reconstitution in HIV-1 Disease
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DOI：
10.1615/critrevimmunol.2022042906
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发表时间：
2021-01-01
影响因子：
1.3
通讯作者：
Leeansyah, Edwin
中科院分区：
文献类型：
--
作者：
Han, Fei;Zheng, Yichao;Leeansyah, Edwin
粘膜相关不变T（MAIT）细胞是一种非传统的先天性1型细胞，它识别由进化上保守的MHC I类相关（MR 1）分子呈递的微生物核黄素相关代谢物。MAIT细胞在循环和粘膜组织中丰富，并且准备针对不同的微生物生物体建立快速效应子应答。尽管没有病毒编码的核黄素相关代谢物抗原，MAIT细胞可以响应于病毒感染的MR 1-独立的和依赖于精氨酸的方式。在慢性HIV-1感染中，MAIT细胞持续耗竭，功能衰竭。长期有效的联合抗逆转录病毒治疗只能部分挽救MAIT细胞数量和功能障碍。我们对HIV-1感染中MAIT细胞损失的机制的理解仍然不完整，迄今为止，几乎没有有效的策略来恢复人类的损失。在这里，我们回顾了目前的知识MAIT细胞反应和损失的机制在HIV-1感染的不同阶段，以及我们如何可能制定战略，以恢复这些细胞在临床环境中。我们进一步讨论了新的策略，可能有助于未来的调查MAIT细胞免疫生物学在HIV-1感染，包括三维类器官模型的潜在用途，解剖MAIT细胞耗竭的机制，并探讨干预措施，可能恢复其数量和功能。
Mucosa-associated invariant T (MAIT) cells are unconventional innate-like 1 cells that recognize microbial riboflavin-related metabolites presented by the evolutionarily conserved MHC class I-related (MR1) molecule. MAIT cells are abundant in circulation and mucosal tissues and are poised to mount rapid effector responses against diverse microbial organisms. Despite the absence of virally encoded riboflavin-related metabolite antigens, MAIT cells can respond to viral infections in an MR1-independent and cytokine-dependent manner. In chronic HIV-1 infection, MAIT cells are persistently depleted and functionally exhausted. Long-term effective combination antiretroviral therapy can only partially rescue MAIT cell numbers and dysfunction. Our understanding of the mechanisms underlying MAIT cell loss in HIV-1 infection is still incomplete, and to date, few effective strategies to recover their loss in humans are available. Here, we review current knowledge concerning the mechanisms of MAIT cell responses and loss in different stages of HIV-1 infection and how we may potentially develop strategies to restore these cells in the clinical setting. We further discuss novel strategies that may aid future investigations into MAIT cell immunobiology in HIV-1 infection, including the potential use of three-dimensional organoid models to dissect the mechanisms of MAIT cell depletion and to explore interventions that may restore their numbers and functionality.