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.

研究表明，常驻记忆CD8 T（Trm）细胞可在小鼠小肠（SI）中提供有效的保护性应答。更好地了解人类中SI CD8 Trm细胞的产生和持久性可能对肠道免疫介导的疾病和疫苗开发有影响。分析正常和移植的人SI，我们证明了大多数SI CD8 T细胞是真正的CD8 Trm细胞，它们在移植物中存活> 1年。上皮内和固有层CD8 Trm细胞表现出高度的克隆重叠性，并以扩大的克隆为主要成分，在肠道和时间上均在空间上保守。在功能上，固有层CD8 Trm细胞是有效的细胞因子生产者，表现出多功能性（IFN-γ ⁺ IL-2 ⁺ TNF-α ⁺），并在刺激后有效表达细胞毒性介质。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标。