School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China.
Helicobacter. 2019 Oct;24(5):e12652. doi: 10.1111/hel.12652. Epub 2019 Aug 14.
Tissue-resident memory T cells accelerate the clearance of pathogens during recall response. However, whether CD4 TRM cells themselves can provide gastric immunity is unclear.
We established a parabiosis model between the enhanced green fluorescent protein and wild-type mice that the circulation system was shared, and the wild-type partner was vaccinated with H pylori vaccine composed of CCF and silk fibroin in gastric subserous layer to induce gastric EGFP CD4 TRM cells. Antigen-specific EGFP CD4 T cells and proliferous TRM cells were analyzed by flow cytometry. The colonization of H pylori was detected by quantitative real-time PCR. EGFP CD4 TRM cells and the inflammation of the stomach were observed by histology.
A parabiosis animal model was employed to identify the cells that introduced by vaccination in GSL. Antigen-specific EGFP CD4 T cells could be detected at day 7 post-vaccination. Thirty days later, EGFP CD4 TRM cells were established with a phenotype of CD69 CD103 . Of note, we found that when circulating lymphocytes were depleted by FTY720 administration, these TRM cells could proliferate in situ and differentiate into effector Th1 cells after H pylori challenge. A decrease in H pylori colonization was observed in the vaccinated mice but not unvaccinated mice. Further, we found that although FTY720 was administrated, mounted pro-inflammatory myeloid cells still emerged in the stomach of the vaccinated mice, which might contribute to the reduction of H pylori colonization.
Our study reveals that H pylori vaccine-induced CD4 TRM cells can proliferate and differentiate in situ to enhance gastric local immunity during recall response.
组织驻留记忆 T 细胞在回忆反应中加速清除病原体。然而，CD4 TRM 细胞本身是否能提供胃免疫尚不清楚。
我们建立了一个增强型绿色荧光蛋白和野生型小鼠的联体模型，共享循环系统，野生型伙伴在胃浆膜下层用由 CCF 和丝素蛋白组成的 Hpylori 疫苗接种，以诱导胃 EGFP CD4 TRM 细胞。通过流式细胞术分析抗原特异性 EGFP CD4 T 细胞和增殖性 TRM 细胞。通过定量实时 PCR 检测 Hpylori 的定植。通过组织学观察 EGFP CD4 TRM 细胞和胃的炎症。
采用联体动物模型来鉴定在 GSL 中接种疫苗引入的细胞。在接种后第 7 天可检测到抗原特异性 EGFP CD4 T 细胞。30 天后，建立了具有 CD69 CD103 表型的 EGFP CD4 TRM 细胞。值得注意的是，我们发现当通过 FTY720 给药耗尽循环淋巴细胞时，这些 TRM 细胞可以在原位增殖，并在 Hpylori 挑战后分化为效应 Th1 细胞。在接种疫苗的小鼠中观察到 Hpylori 定植减少，但在未接种疫苗的小鼠中未观察到。此外，我们发现尽管给予了 FTY720，但接种疫苗的小鼠胃中仍出现大量促炎髓样细胞，这可能有助于减少 Hpylori 定植。
本研究揭示了 Hpylori 疫苗诱导的 CD4 TRM 细胞在回忆反应中可以增殖和分化为效应细胞，从而增强胃局部免疫。
