Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2023 Aug 31;14:1109759. doi: 10.3389/fimmu.2023.1109759. eCollection 2023.
Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease.
Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG.
Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of .
These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.
黏膜相关不变 T（MAIT）细胞是一类先天样 T 细胞，通过识别由微生物核黄素合成衍生的代谢物抗原，并由 MHC-I 相关蛋白 1（MR1）呈递，介导宿主对微生物感染的免疫反应。也就是说，强效的 MAIT 细胞抗原，5-(2-氧代丙基二胺基)-6-D-核糖基尿嘧啶（5-OP-RU）和 5-(2-氧代乙基二胺基)-6-D-核糖基尿嘧啶（5-OE-RU），分别通过核黄素前体 5-氨基-6-D-核糖基尿嘧啶（5-A-RU）与反应性羰基物质（RCS）甲基乙二醛（MG）和乙二醛（G）缩合形成。尽管 MAIT 细胞在人类中丰富存在，但在小鼠中却很少见，并且使用带有抗原和佐剂的扩增方案增加其丰度已被证明有助于在感染和疾病的小鼠模型中研究 MAIT 细胞。
在这里，我们概述了三种方法，通过使用炎症刺激物、5-A-RU 和 MG 的组合，在 C57BL/6 小鼠中增加 MAIT 细胞的丰度。
我们的数据表明，在三种不同的炎症刺激物之一的组合下，给予合成的 5-A-RU 足以增加 C57BL/6 小鼠中 MAIT 细胞的频率和绝对数量。由此产生的增强的 MAIT 细胞是功能性的，可提供针对致命感染的保护。
这些结果为使用高剂量的商业上可获得的 5-A-RU（±MG）在各种危险信号存在下扩增 MAIT 细胞提供了替代方法。
