Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as TLR agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-d-ribitylaminouracil/methylglyoxal. We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-amino-6-d-ribitylaminouracil/methylglyoxal-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation.

中文翻译：

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在T细胞受体介导的人MAIT细胞活化过程中，I型干扰素是重要的共刺激信号。

粘膜相关不变T（MAIT）细胞是丰富的非常规T细胞，可以通过其TCR或先天性细胞因子来刺激。MAIT细胞TCR识别与MR1结合的源自核黄素合成细菌的嘧啶配体。在感染中，细菌不仅提供嘧啶配体，而且还提供可刺激TCR介导的激活的共刺激信号（例如TLR激动剂）。最近，已确定I型干扰素（T1-IFN）有助于细胞因子介导的MAIT细胞活化。然而，未知的是T1-IFN在TCR介导的MAIT细胞活化过程中是否也起作用。在这项研究中，我们调查了T1-IFN在MR1配体5-氨基-6-d-核糖基氨基尿嘧啶/甲基乙二醛的TCR介导的MAIT细胞活化过程中的共刺激作用。我们发现T1-IFNs能够增强5-氨基-6-d-核糖胺基尿嘧啶/甲基乙二醛刺激的MAIT细胞中的干扰素-γ和颗粒酶B的生产。同样，流感病毒诱导的T1-IFNs增强了TCR介导的MAIT细胞活化。还证明了T1-IFN在核黄素合成细菌调控MAIT细胞活化中的重要作用。T1-IFN的共刺激作用在肝源性MAIT细胞中也很明显。T1-IFN直接作用于MAIT细胞，以增强其对TCR刺激的反应。总的来说，我们的发现建立了T1-IFN在TCR介导的MAIT细胞激活过程中的重要免疫调节作用。还证明了T1-IFN在核黄素合成细菌调控MAIT细胞活化中的重要作用。T1-IFN的共刺激作用在肝源性MAIT细胞中也很明显。T1-IFN直接作用于MAIT细胞，以增强其对TCR刺激的反应。总的来说，我们的发现建立了T1-IFN在TCR介导的MAIT细胞激活过程中的重要免疫调节作用。还证明了T1-IFN在核黄素合成细菌调控MAIT细胞活化中的重要作用。T1-IFN的共刺激作用在肝源性MAIT细胞中也很明显。T1-IFN直接作用于MAIT细胞，以增强其对TCR刺激的反应。总的来说，我们的发现建立了T1-IFN在TCR介导的MAIT细胞激活过程中的重要免疫调节作用。