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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. [ABSTRACT FROM AUTHOR]

Background: Toxic adjuvant is considered as an indispensable constituent for oral Helicobacter pylori (H. pylori) vaccines. However, the elaborate role of toxic adjuvant in the initiation of adaptive immune response is largely undescribed. Materials and methods: We employed an acid‐resistant HP55/PLGA nanoparticles (NPs) delivery system encapsulating three antigens (Hsp, Nap, and Lpp20) from H. pylori and accompanied with three adjuvants (LPS, CpG, and chimeric flagellum (CF)) to explore the underlying mechanism of the adjuvant constituent. H. pylori‐specific antibody responses were detected by ELISA. Gastric inflammatory and Th1/Th17 responses were analyzed by flow cytometry. Expressions of inflammatory cytokines were measured by quantitative real‐time PCR. Results: In bone marrow‐derived dendritic cells' (BMDCs) model, the addition of toxic adjuvants is responsible for the proinflammatory function, but not the mature phenotype of BMDCs. In vivo, intestinal loop injection with NPs + LPS, rather than NPs alone, altered the dendritic cell (DC) phenotypes in mesenteric lymph nodes and drove a local proinflammatory microenvironment. In a prophylactic vaccination model, mice immunized with NPs + adjuvants significantly reduced the gastric colonization of H. pylori, induced antigen‐specific antibody responses and Th1/Th17 cell responses. After H. pylori challenge, these mice showed potent recall responses involving both neutrophil and inflammatory monocyte infiltration. Additionally, TLR4 knockout mice were immunized with NPs + LPS and NPs + CF, respectively; only the recipients of NPs + CF orchestrated a protective response to control bacterial infection. Conclusions: Our study indicated that toxic adjuvants within oral H.pylori vaccines altered the function and phenotype of dendritic cells and facilitated the establishment of proinflammatory microenvironment to initiate adaptive immune responses. [ABSTRACT FROM AUTHOR]

High-power piezoelectric ceramics typically operate under severe conditions. This makes the accurate evaluation of their high-power performances through pure quasi-static parameters challenging. The 0.94PbZr 0.5 Ti 0.5 O 3 - 0.06Pb(Mn 1/3 Nb 2/3 )O 3 + 0.005Fe 2 O 3 + 0.002Sc 2 O 3 (PZT-1) ceramic exhibits exceptional and reliable high-power performances at elevated temperatures and under loading conditions. While numerous PZT-based ceramics demonstrate excellent quasi-static parameters, only the PZT-1 ceramic displays superior high-field parameters, such as a low tan δ of 0.97% at 566 V/mm (1 kHz) and a large Q m of 1164 at 50 V/mm (100 kHz). Therefore, the PZT-1 ceramic demonstrates remarkably slow heat generation and the highest surface temperatures are only 41.8 °C at 50 V/mm (100 kHz). Moreover, the PZT-1 ceramic shows a minimal resonance frequency variation of -0.04% in the temperature range of 25-120 °C at 50 V/mm. Consequently, the PZT-1 ceramic maintains a high and reliable vibration velocity of 0.90 m/s at 120 °C for 30 min, and the ceramic cantilever sustains a high amplitude of 7 μm, significantly outperforming other ceramics. This study conclusively demonstrates that high-field parameters, rather than quasi-static parameters, are more effective in accurately estimating the high-power performances of ceramics.

T cell receptor (TCR) engagement causes a global cellular response that entrains signaling pathways, cell cycle regulation, and cell death. The molecular regulation of mRNA translation in these processes is poorly understood. Using a whole-genome CRISPR screen for regulators of CD95 (FAS/APO-1)-mediated T cell death, we identified AMBRA1, a protein previously studied for its roles in autophagy, E3 ubiquitin ligase activity, and cyclin regulation. T cells lacking AMBRA1 resisted FAS-mediated cell death by down-regulating FAS expression at the translational level. We show that AMBRA1 is a vital regulator of ribosome protein biosynthesis and ribosome loading on select mRNAs, whereby it plays a key role in balancing TCR signaling with cell cycle regulation pathways. We also found that AMBRA1 itself is translationally controlled by TCR stimulation via the CD28-PI3K-mTORC1-EIF4F pathway. Together, these findings shed light on the molecular control of translation after T cell activation and implicate AMBRA1 as a translational regulator governing TCR signaling, cell cycle progression, and T cell death., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Toxic adjuvant is considered as an indispensable constituent for oral Helicobacter pylori (H. pylori) vaccines. However, the elaborate role of toxic adjuvant in the initiation of adaptive immune response is largely undescribed., Materials and Methods: We employed an acid-resistant HP55/PLGA nanoparticles (NPs) delivery system encapsulating three antigens (Hsp, Nap, and Lpp20) from H. pylori and accompanied with three adjuvants (LPS, CpG, and chimeric flagellum (CF)) to explore the underlying mechanism of the adjuvant constituent. H. pylori-specific antibody responses were detected by ELISA. Gastric inflammatory and Th1/Th17 responses were analyzed by flow cytometry. Expressions of inflammatory cytokines were measured by quantitative real-time PCR., Results: In bone marrow-derived dendritic cells' (BMDCs) model, the addition of toxic adjuvants is responsible for the proinflammatory function, but not the mature phenotype of BMDCs. In vivo, intestinal loop injection with NPs + LPS, rather than NPs alone, altered the dendritic cell (DC) phenotypes in mesenteric lymph nodes and drove a local proinflammatory microenvironment. In a prophylactic vaccination model, mice immunized with NPs + adjuvants significantly reduced the gastric colonization of H. pylori, induced antigen-specific antibody responses and Th1/Th17 cell responses. After H. pylori challenge, these mice showed potent recall responses involving both neutrophil and inflammatory monocyte infiltration. Additionally, TLR4 knockout mice were immunized with NPs + LPS and NPs + CF, respectively; only the recipients of NPs + CF orchestrated a protective response to control bacterial infection., Conclusions: Our study indicated that toxic adjuvants within oral H.pylori vaccines altered the function and phenotype of dendritic cells and facilitated the establishment of proinflammatory microenvironment to initiate adaptive immune responses., (© 2018 John Wiley & Sons Ltd.)