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The quality of life of organ transplant recipients is closely correlated with immune status. Compared with those undergoing other solid organ transplantation, the long-term prognosis of lung transplant recipients is worse. The underlying immune mechanism is complex with both similarities and characteristics. Therefore, in-depth understanding of the immune mechanism in the process of immune response of allogeneic lung transplantation plays a critical role in improving the long-term survival of the recipients. In this article, the unique composition of immune cells in the lung, the characteristics of rejection after lung transplantation, the early warning and differential diagnosis of pathogen infection in lung transplantation and postoperative complications after lung transplantation were investigated. Research progress on clinical diagnosis and basic studies related to immunology in allogeneic lung transplantation were summarized, aiming to elucidate the immunological characteristics of lung transplantation and provide theoretical basis for improving the longterm survival of lung transplant recipients and prevention and treatment of allograft dysfunction.
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Trogocytosis is a process of exchanging part of the membrane fragment or cytoplasmic content of cells through direct contact, and it's an interaction mechanism that exists between cells. Immune cell can obtain some characteristics of other cells through trogocytosis, and the new cells generated through trogocytosis may play an important role in the induction of graft immune tolerance. In this article, the origin and development of research on cell trogocytosis, mechanism of cell trogocytosis and biological significance of trogocytosis of immune cell were reviewed.
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The liver is an "immune-privileged organ". The incidence and severity of acute rejection after liver transplantation are significantly lower than those after the transplantation of other organs. However, postoperative rejection is still relatively common, and standardized immunosuppressive therapy is the key to guarantee the efficacy of transplantation. To further standardize the immunosuppressive therapy and diagnosis and treatment of rejection after liver transplantation, Branch of Organ Transplantation of Chinese Medical Association organized liver transplant experts to summarize the latest research progress at home and abroad, integrate international guidelines and clinical practice and formulate the "Diagnosis and treatment specification for immunosuppressive therapy and rejection of liver transplantation in China (2019 edition)" based upon the application principle and common regime of immunosuppressant, as well as diagnosis and treatment of various types of rejection after liver transplantation.
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A large quantity of studies related to renal transplantation were reviewed to extract and summarize the international frontier hot spots and difficulties, new transplantation technologies, new methods, new visions and new progress on renal transplantation in 2020.The main contents included rejection, optimization application and regulation of immunosuppression, transplant infection, malignancy after transplantation, non-invasive detection and biomarkers, donor organ preservation, repair and utilization, recurrence of renal disease after renal transplantation, multi-factors affecting long-term survival of transplant kidney, computer and artificial intelligence, etc.Strengthening the reading and thinking of literatures in the field of renal transplantation and broadening horizons in higher starting piont, combined with clinical practice of renal transplantation in China, help to promote the long-term efficacy of renal transplantation.
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Objective To investigate the dynamic changes of peripheral blood lymphocyte subsets and their correlation with renal function in recipients with stable graft status after renal transplantation. Methods Forty-five recipients who underwent renal transplantation for the first time and had stable graft function within postoperative 6 months were selected. The proportion and absolute value of lymphocyte subsets were detected by flow cytometry (FCM) in 180 peripheral blood samples from recipients at 15 d, 1, 3 and 6 months after renal transplantation. The dynamic changes of lymphocyte subsets with the extension of postoperative time and their correlation with serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed. Results The Scr levels did not significantly differ at 4 time points after renal transplantation (all P > 0.05). The BUN levels significantly differed between 15 d and 1 month after renal transplantation, and between 1 and 3 months after renal transplantation (P=0.002, P=0.001). The proportion of CD3+CD8+T cells, CD3+CD4+T cells, natural killer (NK) cells and CD4/CD8 ratio at postoperative 15 d significantly differed from those at 1 month after operation (P=0.009, P=0.004, P < 0.001, P=0.004). The proportion of B cells significantly differed between 15 d and 1 month, and between 1 and 3 months after renal transplantation (both P < 0.001). The absolute values of CD3+T cells, CD3+CD8+T cells, CD3+CD4+T cells and NK cells at postoperative 15 d significantly differed from those at 1 month after renal transplantation (P=0.001, P=0.002, P=0.003, P < 0.001). The absolute values of CD3+CD8+T cells significantly differed between 3 and 6 months after operation (P=0.015). The absolute value of B cells at 1 month after renal transplantation significantly differed from that at 3 months after renal transplantation (P=0.001). The proportion and absolute value of lymphocyte subsets were not significantly correlated with the Scr level (both P > 0.05). The proportion and absolute value of CD3+CD8+T cells and NK cells were negatively correlated with BUN (P < 0.001-0.05), whereas the proportion of CD3+CD4+T cells and B cells was positively correlated with the BUN level (P < 0.001-0.05). The absolute value of CD3+T cells was negatively associated with the BUN level (P < 0.05). Conclusions T cells and NK cells in the lymphocyte subsets of stable recipients raise to the stable state within 1 month after renal transplantation, whereas B cells decrease to stable state within 3 months renal transplantation. The dynamic changes of lymphocyte subsets are correlated with the BUN level.
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Objective To investigate the regulating function of human gingival mesenchymal stem cell (GMSC) on the proliferation and differentiation of B cells and its underlying molecular mechanism. Methods GMSC were isolated and B cells were isolated from peripheral blood. GMSC or fibroblasts were co-cultured with B cells in vitro and assigned into the GMSC group and fibroblast group. The proliferation of B cells was detected in two groups. The expression of IgG1 and IgM in the cell supernatants was measured between two groups. The secretion of interleukin (IL)-6, Perforin, interferon (IFN)-γ and tumor necrosis factor (TNF)-α was compared between two groups. The expression levels ofIL-10 and transforming growth factor (TGF)-β in B cells were detected between two groups. The expression of PC-1 in B cells was measured in two groups. The signaling pathway involved with the regulating effect of GMSC on B cell function was investigated. The regulating effect of GMSC on the role of B cells in activating T cell function was assessed. Results Compared with the fibroblast group, the proliferation of B cells was significantly weakened in the GMSC group (P < 0.05). Co-culture of GMSC and B cells significantly inhibited the secretion of IgG1 and IgM from B cells and the secretion ofIL-6, Perforin, IFN-γ and TNF-α (all P < 0.05). Compared with the fibroblast group, the secretion of IL-10 and TGF-βwas significantly higher in the GMSC group (both P < 0.05). The expression level of PC-1 in the GMSC group was significantly down-regulated (P < 0.05). After adding ALK5, an inhibitor of TGF-β receptor, the inhibitory effect of GMSC upon B cells was significantly weakened (P < 0.05). Compared with the fibroblast group, the ability of B cells to activate and proliferate T cells was significantly attenuated in the GMSC group (P < 0.05). Conclusions GMSC can inhibit B cells and their mediated immune responses. The activation of B cells and other related functions can be suppressed through the TGF-β signaling pathway.
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In this paper, forefront hotspots in clinical and applied basis of organ transplantation as well as translational medicine during 2019 American Transplant Congress (ATC) were summarized. It involved transplantation clinical priorities and difficulties which were concerned by transplant surgeons. These hot topics included the immunological mechanisms, risk factors, prognosis evaluation and important biological markers of donor specific antibody (DSA) and antibody-mediated rejection (AMR), desensitization strategy in highly sensitized patients and progress of AMR prevention and treatment, current status and development direction of clinical immune tolerance, hotspots and prevention progress on transplantation-related infection, and brief evaluation of various donor organ mechanical perfusion methods, etc.
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Rejection is the main cause of transplantation failure. Currently, the specificity and sensitivity of clinical parameters are relatively poor, which cannot accurately prompt the exact cause of rejection. It is of great clinical significance to explore novel biomarkers for monitoring the rejection. In this article, the latest research progress on the biomarkers of rejection risk in organ transplantation were summarized from the perspectives of transplantation pathology, immune cells and regulatory immune cells, non-human leukocyte antigen antibodies, exosomes, cell-free DNA and combination gene prediction, aiming to provide reference for early warning and treatment of rejection in organ transplantation.
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Myeloid-derived suppressor cell (MDSC) is a type of heterogeneous cell derived from bone marrow, which was first found in tumor. MDSC can inhibit the function of T cell with immunosuppressive effect. In recent years, more and more studies have shown that in the field of organ transplantation, MDSC can also regulate the host's immune function, induce specific immune tolerance, and play a protective role in transplant organs, which is expected to become a new target in clinical treatment of transplant rejection. The biological characteristics of MDSC and the mechanism of immune tolerance induced by MDSC were reviewed in this paper.
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Xenotransplantation is the most promising method to resolve the organ shortage problem in the future. In recent years, the advances in gene editing and immunological technique have driven the rapid development of xenotransplantation. However, there are still many insurmountable obstacles in the clinical application of xenotransplantation, among which the rejection is the most important cause of the xenotransplantation failure. Regulatory immunological cells are a group of immunological cells with the negative regulation function in the body, which can inhibit allotransplantation rejection and prolong the survival time of the graft. This paper summarized the research progress of regulatory immunological cells in the xenotransplantation application in recent years, providing reference for the prevention and treatment of xenotransplantation rejection.
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Objective To analyze the characteristics of papers published in Organ Transplantation in the past ten years. Methods The academic papers published in Organ Transplantation from January 2010 to December 2019 were retrieved from China National Knowledge Infrastructure (CNKI). The publication volume, the funded paper ratio, authors, research institutions and keywords were analyzed by information visualization software CiteSpace 5.3 and VOSviewer 1.6. Results From 2010 to 2019, a total of 919 academic papers were published in Organ Transplantation, with an average annual publication volume of 92, showing an overall stable trend. The funded paper ratio and the ratio of papers with funding support at the provincial level or above increased year by year, reaching 100% in 2019. High-yield authors mainly formed two research teams led by Shi Bingyi and Chen Guihua respectively. The first authors were distributed across China. In recent years, as many as 58 programmatic papers were published by national academic institutions, especially signed by Branch of Organ Transplantation of Chinese Medical Association. The average number of authors per paper was 4.94 in Organ Transplantation, and the proportion of papers contributed by two or more authors remained above 90% in recent years. According to the analysis of research institutions, the average number of institutions per paper was 1.60 in Organ Transplantation. Keyword co-occurrence network analysis demonstrated that liver transplantation, renal transplantation and organ transplantation were the research hotspots in the field of organ transplantation. Keyword cluster analysis showed that research mainly focused on 9 fields, such as liver transplantation, renal transplantation, organ transplantation, organ donation, posttransplantation complications, transplantation immunity, end-stage liver disease, xenotransplantation and stem cell transplantation. Keyword burst analysis showed that xenotransplantation, α-1, 3-galactose, transplantation immunity, apoptosis, donor specific antibody (DSA), antibody-mediated rejection (AMR) and flow cytometry were the research hotspots. Conclusions The authors that publish academic papers in Organ Transplantation come from major transplantation centers all over the country. The papers of Organ Transplantation cover the research hotspots of each branch in the field of organ transplantation, and include a large quantity of programmatic papers signed and published by national academic institutions, which show the frontier hotspots and the highest level of research in the field of organ transplantation in China, making Organ Transplantation an excellent academic journal.
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The induction of immune tolerance is an essential component and the utmost goal in the field of organ transplantation immunity, which depends upon the recognition and presentation of transplantation antigens, the activation and response of the immune system and other immune essence. However, before successfully inducing immune tolerance, how to carry out individualized induction of immune tolerance in organ transplant recipients to optimize the combination of immunosuppressive agents and individualized treatment and achieve the ideal state of optimal prevention and treatment of immune rejection and minimal adverse reactions, remains to be further resolved by the organ transplantation practitioners. Based on the reports of international core journals, the individualized induction strategy of immune tolerance and the future prospects were reviewed in this article from the following aspects including the mechanism underlying induction of immune tolerance, realization of operational immune tolerance, novel strategy of individualized induction of immune tolerance and application of regulatory T cell in individualized immune tolerance in combination with clinical and laboratory research results of regulatory T cell in our center.
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Objective To summarize the practice experience of establishing a stable abdominal heart transplantation model combined with tail vein injection in mice. Methods In the preliminary experiment, 50 pairs of donor and recipient Kunming mice received isotransplantation, 40 pairs of donor and recipient C57BL/6J mice underwent isotransplantation. In the formal experiment, 10 pairs of donor and recipient C57BL/6J mice received isotransplantation, 30 pairs of Balb/c mice as the donor and C57BL/6J mice as the recipient received allotransplantation. The time of each step of the heart transplantation (including harvesting and dressing of the donor heart, vascular anastomosis of the recipient, etc.) was recorded. The duration of transplanted heart beat and the survival time of the recipient was observed daily after operation. The time required for tail vein injection in the transplanted mice was recorded. Pathological examination of the transplanted heart was performed at 30 d after isotransplantation (n=5) and 7 d after allotransplantation (n=5). Results In the formal experiment, the success rate of heart transplantation was 90%. The harvesting and dressing time of donor heart was (13.9±0.6) min. The cold ischemia time of the recipient was (14.2±1.2) min. The vascular anastomosis time was (34.2±3.1) min. The total operation time was (86.6±5.4) min. Postoperatively, the transplanted heart of the mice undergoing isotransplantation survived longer than 100 d. Pathological examination at postoperative 30 d demonstrated only a slight amount of inflammatory cell infiltration. The survival time of the mice receiving allotransplantation was (7.2±0.5) d due to rejection reaction. At postoperative 7 d, pathological examination showed a large quantity of inflammatory cells infiltrating into the myocardium, manifested with acute cellular rejection. The success rate reached 90% after over 200 times of tail vein injection. Conclusions In this study, a stable mouse abdominal heart transplantation model is successfully established. The mouse models in the preliminary experiment can be utilized for tail vein injection.
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Objective To investigate the effect of regulatory dendritic cells treated by extracorporeal photochemotherapy on T cell proliferation. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained and the immature dendritic cells (imDCs) were induced by recombinant human granulocyte and macrophage colony stimulating factors. SPDCs were obtained by PUVA treatment, and ECDCs were co-cultured with imDCs and PUVA-SP to obtain immunoprecipitated dendritic cells. In vitro, imDCs were co-cultured with SPDCs to obtain SPDCs; imDCs were added to 10ng/ml of LPS, and cultured for 1 day to obtain DCs. The expressions of CD11c, CD83 and CD86 on the surface of the cells were detected. The effect of imDCs on the proliferation of recipient T cells was detected by mixed lymphocyte culture method. Results The early apoptosis rate of PUVA-treated cells was 91.33%. The positive expression rates of CD83 and CD86 in ecpDCs were 22.83%±5.26% and 22.06%±4.37%, respectively, which were similar to those of imDCs (15.06%±0.59%, 15.19%±1.83% (P<0.01), but significantly lower than those in DCs (99.79%±0.36%, 99.85%±0.19%, respectively), the difference was statistically significant (P<0.01). The recipient imDC cells phagocyting the appoptotic splenic lymphocytes from the donor significantly inhibited the proliferation of recipient T cells. Conclusion Apoptosis of splenic lymphocytes induced by extracorporeal photochemotherapy can inhibit the maturation of dendritic cells and inhibit the proliferation of T lymphocytes.
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Objective To evaluate the effect of γ-aminobutyric acid (GABA) and its receptors upon the proliferation of CD8+T cells.Methods The splenic CD8+T cells of Balb/c mice were obtained by CD8+f cell magnetic bead sorting kit.Under the effect of CD3/CD28-activated magnetic bead,CD8+T cells were stimulated by different concentrations of GABA.5-bromo-2-deoxyuridine (BrdU) labeling and flow cytometry were performed to detect the proliferation of CD8+T cells.The expression levels of GABA-A and GABA-B receptor before and after CD8+T cell activation were compared by fluorescent quantitative real-time polymerase chain reaction (PCR).Result Flow cytometry result revealed that GABA could inhibit the proliferation of activated CD8+T cells,manifested as significant decrease in the quantity of CD152+CD8+T cells.Fluorescent quantitative real-time PCR demonstrated that GABA-A receptor subtypes α2,α6 and GABA-B receptor subtype 1a were expressed only when the CD8+T cells were activated.After CD8+T cell activation,the quantity of GABA-A receptor subtypes α3,αs,β2,β3,γ1,γ2 and θ were significantly increased,whereas the quantity of GABA-B2R and GABA-B1b did not significantly differ before and after CD8+T cell activation.Conclusions GABA can suppress the proliferation of activated CD8+T cells.The activation of CD8+T cells is regulated by GABA receptors.However,the underlying mechanism remains to be elucidated.
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0.05). Conclusion:Certain concentration of TG can inhibit the apoptosis of Schwann’s cell and the expression of major histocompatibility antigen of cold preserved sciatic nerve in rats,and decrease rejection after nerve allograft.
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Objective To observe the impact of transplant nephrectomy on panel reactive antibodies and a secondary renal transplantation.Methods Panel reactive antibodies in 15 patients with a failed renal transplant admitted in our hospital between 2004 to 2007 were measured before transplantation,before and 1 month,6 months,12 months after transplant nephrectomy,and the pathological changes were observed after transplant nephrectomy.Results Panel reactive antibodies was increasing after renal transplantation,and reached the highest level one month after transplant nephrectomy,then grandually got down.New HLA allosensitization sites were discovered after transplant nephrectomy.Large amount of C4d was stained in failed transplant.Conclusion Serum PRA increased after transplant nephrectomy.New HLA allosensitization sites were found,which may be useful in HLA matching.