Department of Microbiology and Immunology, University of Otago, Dunedin 9016, Otago, New Zealand.
School of Pharmacy, University of Otago, Dunedin 9016, Otago, New Zealand.
Cell Rep. 2019 Sep 17;28(12):3061-3076.e5. doi: 10.1016/j.celrep.2019.08.054.
Mucosal-associated invariant T (MAIT) cells can be activated via either their T cell receptor (TCR), which recognizes MR1-bound pyrimidines derived from microbial riboflavin biosynthesis, or via cytokines. These two modes of activation may act in concert or independently, depending upon the stimulus. It is unknown, however, how MAIT cell responses differ with the mode of activation. Here, we define transcriptional and effector responses of human CD8 MAIT cells to TCR and cytokine stimulation. We report that MAIT cells rapidly respond to TCR stimulation, producing multiple cytokines and chemokines, altering their cytotoxic granule content and transcription factor expression, and upregulating co-stimulatory proteins. In contrast, cytokine-mediated activation is slower and results in a more limited response. Therefore, we propose that, in infections by riboflavin-synthesizing bacteria, MAIT cells play a key early role in effecting and coordinating immune responses, while in the absence of TCR stimulation, their role is likely to differ.
黏膜相关恒定 T（MAIT）细胞可通过其 T 细胞受体（TCR）被激活，该受体识别来自微生物核黄素生物合成的 MR1 结合嘧啶，或者通过细胞因子被激活。这两种激活方式可能协同作用或独立作用，具体取决于刺激物。然而，目前尚不清楚 MAIT 细胞的反应如何因激活方式的不同而不同。在这里，我们定义了人类 CD8 MAIT 细胞对 TCR 和细胞因子刺激的转录和效应反应。我们报告说，MAIT 细胞对 TCR 刺激迅速作出反应，产生多种细胞因子和趋化因子，改变其细胞毒性颗粒含量和转录因子表达，并上调共刺激蛋白。相比之下，细胞因子介导的激活较慢，导致反应更有限。因此，我们提出，在合成核黄素的细菌感染中，MAIT 细胞在启动和协调免疫反应方面发挥关键作用，而在缺乏 TCR 刺激的情况下，其作用可能有所不同。
