组织驻留记忆T细胞（TRM）可增强疫苗介导的黏膜免疫保护。研究表明，幽门螺旋杆菌（Hp）疫苗介导的免疫保护，不仅依赖于辅助T细胞应答，与原位免疫记忆缺失也休戚相关。胃TRM细胞具有组织定位优势，能够诱导敏感迅捷的免疫反应，增强疫苗效果，是目前Hp疫苗研究的重要方向。因此，课题组尝试在小鼠胃浆膜层接种铝剂Hp疫苗CCF，研究胃部预设Hp特异性的TRM细胞的可能性；初步证实浆膜接种CCF能够诱导接种处附近胃上皮TRM（CD4+T）的形成。在此基础上，本项目拟以生物相容性材料为载体, 优化TRM在胃部的形成，构建稳定的TRM研究小鼠模型；采用组织免疫荧光技术、流式细胞分选分析和体内中和抗体阻断实验，揭示TRM细胞胃上皮黏膜迁移、形成及驻留的具体作用机制；采用联体小鼠模型，对比胃部TRM与循环记忆细胞免疫保护效果差异，确证TRM免疫保护优势。这些研究目标的实现，能够为Hp疫苗的研发提供新的思路。

Tissue-resident memory T cells (TRM) enhance vaccine-induced immune protection, especially in peripheral tissues. Clinical and preclinical trials studies indicated that Helicobacter pylori (H. pylori) vaccines conferred protection dependent on the engagement of CD4+T cellular immune response. Yet, induction of TRM in stomach requires regional antigen exposure, which to date none study makes an attempt. Gastric TRM with advantage in location can trigger a swift recall response to enhance H. pylori clearance. We tried to establish a pool of vaccine-induced TRM in stomach by using gastric subserous layer vaccination and Alum-based vaccine. The preliminary data showed that a pool of intraepithelial TRM was located on adjacent mucosa. Here, we plan to replace Alum adjuvant by biocompatible materials to extend TRM distribution. The mechanism of how CD4+T cells migrate to epithelium and form a pool of TRM is explored in this model by using immunofluorescent histology, flow cytometry, and neutralizing antibody experiments. The superiority of TRM is investigated in parabiosis mice. This study sheds a new light on the field of H. pylori vaccine and provides evidence for the development of an effective vaccine against mucosal pathogens.