Vaccine-induced gastric CD4+ tissue-resident memory T cells proliferate in situ to amplify immune response against Helicobacter pylori insult.

ABSTRACT

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.