ImmunoSurveillance Lab, The Francis Crick Institute, London, NW1 1AT, UK.
Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, SE1 9RT, UK.
Mucosal Immunol. 2020 Nov;13(6):969-981. doi: 10.1038/s41385-020-0305-7. Epub 2020 May 29.
This most comprehensive analysis to date of γδ T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1 T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6, IFN-γ-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, γδ T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.
这是迄今为止对鼠类子宫γδ T 细胞最全面的分析,揭示了它们构成了一个独特的局部 T 细胞区室。与早期报道一致,大多数细胞表达典型的 Vγ6Vδ1TCR,并在受到刺激后产生白细胞介素(IL)-17A。然而,与早期报道不同的是,子宫γδ T 细胞并非明显的上皮内细胞,而更类似于其他几个解剖部位的上皮下 Vγ6Vδ1T 细胞。然而,与其他组织不同的是,子宫腔还包含非 Vγ6、产生 IFN-γ 的细胞;在幼鼠中明显丰富;表达以前与子宫相关的基因,包括孕激素受体;并且其发育和/或维持不需要微生物。尽管如此,γδ T 细胞缺陷严重损害了对阴道假丝酵母菌感染的抵抗力,与依赖 IL-17 的中性粒细胞反应降低有关。这些发现强调了不同黏膜 γδ 细胞区室的组织特异性复杂性,以及它们在针对屏障感染的淋巴应激监测中的明显重要性。