Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway
Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway.
J Exp Med. 2019 Oct 7;216(10):2412-2426. doi: 10.1084/jem.20190414. Epub 2019 Jul 23.
Resident memory CD8 T (Trm) cells have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI, we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for >1 yr in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine producers, exhibiting a polyfunctional (IFN-γ IL-2 TNF-α) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.
驻留记忆 CD8 T（Trm）细胞已被证明能在小鼠的小肠（SI）中提供有效的保护反应。更好地了解人类 SI CD8 Trm 细胞的产生和持续存在可能对肠道免疫介导的疾病和疫苗开发具有重要意义。分析正常和移植的人 SI，我们证明大多数 SI CD8 T 细胞是真正的 CD8 Trm 细胞，在移植物中存活超过 1 年。上皮内和固有层的 CD8 Trm 细胞显示出高度的克隆重叠，其表型由空间上在肠道中以及随时间推移而保守的扩增克隆主导。功能上，固有层的 CD8 Trm 细胞是有效的细胞因子产生细胞，表现出多能（IFN-γ IL-2 TNF-α）表型，并且在刺激后能有效地表达细胞毒性介质。这些结果表明，SI CD8 Trm 细胞可能是未来口服疫苗和肠道疾病治疗策略的相关靶点。
