Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant T cell receptor, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of over 76,000 human MAIT cells during acute and chronic antigen-specific activation with the MR1 ligand 5-OP-RU and non-specific TCR stimulation. We show that MAIT cells span a broad range of homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4+ or CD8+ co-expression. During acute activation, MAIT cells rapidly adopt a cytotoxic phenotype characterized by high expression of GZMB, IFNG and TNF. In contrast, chronic stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. These scRNAseq-defined MAIT cell subtypes were also detected in individuals recently exposed to Mycobacterium tuberculosis infection, confirming their presence during human infection. Our study provides the first comprehensive atlas of human MAIT cells in activation conditions and defines substantial functional heterogeneity, suggesting complex roles in health and disease.

中文翻译：

---

单细胞转录分析揭示了在稳态和激活过程中富集的辅助，效应和调节性MAIT细胞群体

粘膜相关不变T（MAIT）细胞是先天性淋巴细胞，可识别微生物的维生素B代谢产物，并在传染病，自身免疫性疾病和癌症中起着新的作用。尽管MAIT细胞是由半不变的T细胞受体识别的，但它们的表型和功能异质性尚不十分清楚。在这里，我们介绍了在MR1配体5-OP-RU和非特异性TCR刺激的急性和慢性抗原特异性激活过程中，超过76,000个人MAIT细胞的综合单细胞转录组学分析。我们显示，MAIT细胞跨越广泛的稳态，效应子，辅助，组织浸润，调节和疲惫表型，并具有与CD4 +或CD8 +共表达相关的独特基因表达程序。在急性激活期间，MAIT细胞迅速采用以GZMB，IFNG和TNF高表达为特征的细胞毒性表型。相反，慢性刺激诱导异质状态，其由增殖，细胞毒性，免疫调节和力竭定义。这些scRNAseq定义的MAIT细胞亚型也在最近暴露于结核分枝杆菌感染的个体中检测到，证实了它们在人类感染过程中的存在。我们的研究提供了活化条件下人类MAIT细胞的第一个综合图集，并定义了实质性的功能异质性，暗示了在健康和疾病中的复杂作用。这些scRNAseq定义的MAIT细胞亚型也在最近暴露于结核分枝杆菌感染的个体中检测到，证实了它们在人类感染过程中的存在。我们的研究提供了活化条件下人类MAIT细胞的第一个综合图集，并定义了实质性的功能异质性，暗示了在健康和疾病中的复杂作用。这些scRNAseq定义的MAIT细胞亚型也在最近暴露于结核分枝杆菌感染的个体中检测到，证实了它们在人类感染过程中的存在。我们的研究提供了活化条件下人类MAIT细胞的第一个综合图集，并定义了实质性的功能异质性，暗示了在健康和疾病中的复杂作用。