人类MAIT细胞抑制全活性T细胞的反应,并防止急性移植对宿主疾病的发生
Nana Talvard-Balland1, Marion Lambert1, Mathieu F Chevalier1
1INSERM UMR-976 HIPI, Saint Louis Research Institute, Université Paris Cité, Paris, France.
JCI insight
|February 1, 2024
概括
粘膜相关的不变T细胞 (MAIT) 在预防和治疗移植对宿主疾病 (GVHD) 中表现有前途. 在临床前模型中,MAIT细胞的采用转移有效控制了GVHD,表明它们的治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 移植科学 移植科学
- 细胞疗法细胞疗法
背景情况:
- 移植与宿主疾病 (GVHD) 是全原造血细胞干细胞移植后的一个主要并发症.
- 粘膜关联不变T细胞 (MAIT) 已经证明了组织修复能力,并与人类减少GVHD发病率有关.
研究的目的:
- 在一个体外全活性模型中研究MAIT细胞的免疫抑制潜力.
- 在临床前异种性GVHD模型中评估MAIT细胞采用转移的疗效.
主要方法:
- 在体外分析MAIT细胞对全活性T细胞增殖和激活的影响.
- 使用免疫缺陷小鼠和人类外周血液单核细胞 (PBMCs) 的临床前异源性GVHD模型.
- 对MAIT细胞时间 (早期转移与延迟转移) 对GVHD发病和严重性的评估.
主要成果:
- 新净化和扩张的MAIT细胞以剂量依赖的方式抑制了全活性T细胞的增殖和激活.
- 采用MAIT细胞的转移延迟了GVHD的发病,并减少了小鼠的严重程度,无论转移时间如何.
- MAIT细胞治疗降低了受影响组织的T细胞增殖和效应器功能,与改变的细胞因子概况相关 (IFN-γ/TNF-α较低,IL-10较高).
- MAIT细胞的作用部分通过涉及T细胞受体和MR1的接触依赖相互作用来调解.
结论:
- MAIT细胞具有重要的免疫抑制性质,可控制GVHD.
- 这些发现支持对MAIT细胞进行临床研究,作为治疗严重GVHD和粘膜炎症的通用细胞疗法.
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