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Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
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Transplant rejection involves natural immune cells and acquired immune cells. For decades, acquired immune cells have been dominating the study of transplant immunity. Researchers have found the surprising new features of innate immune cells, including immune memory, which may be of great significance to further improve graft survival. The short-term survival rate of grafts is very good, but the long-term graft outcomes are less so and most transplants are eventually lost to chronic rejection in the clinic. In animal models and clinical studies, innate immune cells, especially macrophages and natural killer cells, often predominate the chronic rejection process which lead grafts lost. Recent studies suggest that innate immune cells are capable of acquiring adaptive features in that they either directly recognize the allografts or become "trained" in the allogeneic milieu to further acquire features of memory and donor specificity. In selected transplant models, targeting the adaptive features of innate immune cells has been shown to promote long-term graft survival. Clearly, these findings highlight new therapeutic opportunities in further improvement of transplant outcomes as well as in treatment of cancers and autoimmune diseases in the clinic. The authors summarize the literature reports, introduce the recent acquired response characteristics of natural immune cells, and stimulate researchers to carry out more exploration in this field by fully discussing the heterogeneity and plasticity of natural immune cell types and the outstanding problems in related field.
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The COVID-19 pandemic has become a serious global public health threat with more than 540 million infections and 6.32 million cases of death as of 25 June, 2022. Understanding whether COVID-19 patients can obtain persistent immune protection after recovery is crucial for vaccine development, disease control and epidemic forecast. The persistent immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is mainly derived from the immune memory. Thus, the generation and maintenance of immune memory specifically targeted to the virus were reviewed in this paper.
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The American Transplant Congress (ATC) is an annual international academic conference in the field of transplantation, which includes the latest achievements of scholars around the world in transplantation, and also leads the frontier direction of transplantation research. In this paper, the international forefront hotspots in basic and translational medicine research associated with renal transplantation in 2020 ATC were summarized, including the new discoveries of memory cell function and immune memory mechanism, the latest discovery in the mechanism of rejection and immune tolerance, the current research status of xenotransplantation, the potential solutions of antibody-mediated rejection (AMR), and the application of nanomedicine and single-cell RNA sequencing in renal transplantation, etc.
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Objective@#To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults.@*Methods@#The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose).@*Results@#The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; β (95%CI) was -0.07 (-0.34-0.20), P=0.601.@*Conclusion@#The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.
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To determine the duration of protection conferred by the hepatitis B (HB)vaccination and the necessity of a booster dose. Methods: Immediately after the initial bloodsampling, 252 youths (aged 18.8-20.5 years, 52% females) with a history of neonatal HBvaccination with one dose of the HB vaccine received a booster. Serum concentrations ofantibodies against the HB surface antigen were assessed in samples collected before and10-14 days after the booster. Seroconversion from concentrations <10 to ?10 IU/L weredefined as a positive immune response. Results: Of the 252 participants, 131 were sero-susceptible and 114 responded. Conclusions: Nearly 90% of young people preserved theirlong-term protection; the results of this study do not support the use of an HB boostervaccination
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Objective:To elucidate the characterization of CD8+T cell in H1N1 influenza vaccine for children.Methods:PBMCs were isolated from 31 children aged from 3 to 6 years old who had accepted H 1N1 influenza vaccine during December 2009 to January 2010.The lymphocytes were joined with the H 1N1 influenza vaccine as experimental group and cultured .The experiment set without vaccine group as control group .At last we detected the surface molecules by FCM .The CCK-8 assay was added to detecting cellular proliferation and cellular proliferation index were detected by CCK-8.Results: CD8+T cells of PBMC in the two groups were 13.41%and 9.41%,P>0.05.CD8+CD45RAA+naive T cells in the two groups were up to more than 80%,P>0.05.The proportion of CD8+CD45ROA+memory T cells in two groups were up to 17%-19%,P>0.05.Two subsets of CD8+CD45ROA+memory T cells :CCR7+and CD62L+single positive memory T cell subsets in the experimental group were significantly lower than that of the control group,P<0.05.The CCK-8 assay was added to detect cellular proliferation .Only 51.16% of which cellular proliferation index was greater than 0.8,with none was greater than 1 in this study.Conclusion:This study showed that the CD4+T cells were low-level,naive T cells (CD8+CD45RAA+)were higher,with antigen stimulation and response.H1N1 vaccination specific memory T cells were few in number , specific memory T cell subsets were diversity , control memory cells were the main phenotypic characteristics .Cellular proliferation index showed that the proliferation of specific CD 8+T cells vaccine was poor .
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Bone marrow is a hematological and immunological organ that provides multiple immune cells, including B lymphocytes, and thus plays a critical role in the efficacy of vaccine. We previously demonstrated that Bordetella (B.) bronchiseptica antigen has high immunogenicity in spleen cells, a peripheral immune organ. In this study, we investigated the immunogenicity of B. bronchiseptica antigen in bone marrow cells, a central immune organ. B. bronchiseptica antigen increased the cellular activity of bone marrow cells and significantly enhanced the production of nitric oxide, IL-6, and TNF-alpha. Bone marrow cells primed with B. bronchiseptica antigen in vivo were harvested and stimulated with the same antigen in vitro. The stimulation of B. bronchiseptica antigen significantly increased the cellular activity and proliferation rate of the primed cells. B. bronchiseptica antigen also greatly induced the production of antigen-specific antibody in the primed cells. Taken together, the present study demonstrated that B. bronchiseptica antigen can stimulate bone marrow cells, a central immune organ, and recall the immune response of the primed bone marrow cells.
Subject(s)
B-Lymphocytes , Bone Marrow , Bone Marrow Cells , Bordetella , Bordetella bronchiseptica , Interleukin-6 , Memory , Nitric Oxide , Spleen , Tumor Necrosis Factor-alphaABSTRACT
Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and effector-triggered immunity (ETI). MTI confers basal resistance, while ETI confers durable resistance, often resulting in hypersensitive response. Plants also possess systemic acquired resistance (SAR), which provides long-term defense against a broad-spectrum of pathogens. Salicylic-acid-mediated systemic acquired immunity provokes the defense response throughout the plant system during pathogen infection at a particular site. Trans-generational immune priming allows the plant to heritably shield their progeny towards pathogens previously encountered. Plants circumvent the viral infection through RNA interference phenomena by utilizing small RNAs. This review summarizes the molecular mechanisms of plant immune system, and the latest breakthroughs reported in plant defense. We discuss the plant–pathogen interactions and integrated defense responses in the context of presenting an integral understanding in plant molecular immunity.