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Lymphocyte infiltration and activation in iris-ciliary body and anterior chamber of mice in corneal allograft rejection

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International Journal of Ophthalmology(English edition) 2012年第6期5卷 681-686页

作者： Fu-Hua Wang Min Chen Ting Liu Xin-Jie Zang Hua-Qing Gong Wei-Yun Shi Qingdao University Medical College Shandong Eye Hospital Shandong Eye Institute Shandong Academy of Medical Science Qingdao Eye Hospital Shandong Eye Institute Shandong Academy of Medical Science State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute Shandong Academy of Medical Sciences

AIM: To investigate the infiltration and activation of lymphocyte in iris-ciliary body and anterior chamber after allogenic penetrating keratoplasty (PK), for further revealing the role of iris-ciliary body in corneal allograft immune rejection. METHODS: In the mice models of PK, BALB/C mice received orthotopic isografts (n =35) or C57BL/6 donor allografts (n=25). grafts were examined daily for 3 weeks by slit-lamp microscopy and scored for opacity. The infiltration of CD4(+) T lymphocyte in iris-ciliary body and anterior chamber was examined by immunohistology and the mRNA of CD80 and CD86 in both cornea graft and iris-ciliary body by RT-PCR was analyzed in allograft recipient at days 3, 6, 10 and the day when graft rejection occurred. Isograft recipients were examined as control at the corresponding time points. Transmission electron microscope was used to study the ultrastructure, especially cell infiltration, of iris-cilary body and corneal graft at day 3, 7 and the day when rejection occurred after allogenic PK. RESULTS: rejection was observed in all the allograft recipients followed more than 10 days, at a median time of 15 days (range 12-18 days), but not in any of isografts. CD4(+) T cells were first detected at day 6 after transplantation in limbus and Ciliary body, and then in the stroma of recipient, iris, anterior chamber and corneal allograft with an increased number until graft rejection occurred. CD80 and CD86 mRNA were detected under RT-PCR examination in both graft and iris-ciliary body of allograft recipient, but not in any of isograft recipient. Three days after operation, lymphocytes and monocytes macrophages were visible in iris blood vessels and the anterior chamber, and vascular endothelial cell proliferation and activation were significant under transmission electron microscopy examination. At day 7, corneal endothelial cells became thinner. Lymphocytes and mononuclear macrophages were found with great number in the anterior chamber and adher

关键词： lymphocyte corneal transplantation penetrating graft rejection iris-ciliary body anterior chamber

The critical role of therapeutic plasma exchange in ABO-incompatible liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 538-542页

作者： Cheng-Zuo Han Qiang Wei Meng-Fan Yang Li Zhuang Xiao Xu Department of Hepatobiliary and Pancreatic Surgery The Center for Integrated Oncology and Precision MedicineAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310022China

Background:The shortage of donor liver restricts liver transplantation(LT).Nowadays,donor liver with ABO blood group incompatibility between donor and recipient has become an option to expand the source of donor *** it is now possible to perform ABO-incompatible(ABO-I)LT,antibody-mediated rejection(AMR)has been recognized as the primary cause of desperate outcomes after ABO-I ***-A/B antibody is the trigger of immune response to ABO-I LT graft *** plasma ex-change(TPE)can quickly reduce the titer of plasma antibodies and effectively inhibit humoral *** sources:We searched PubMed and CNKI databases using search terms“therapeutic plasma ex-change”,“ABO-incompatible liver transplantation”,“ABO-I LT”,“liver transplantation”,“LT”,“antibody-mediated rejection”,and“AMR”.Additional publications were identified by a manual search of references from key *** relevant publications published before September 30,2020 were included in this ***:Different centers have made different attempts on whether to use TPE,when to use TPE and how often to use ***,the control standard of lectin revision level is always controversial,the target titer varies significantly from center to center,and the standard target titer has not yet been *** has several schemes to reduce antibody titers,but there is a lack of clinical trials that provide standardized ***:TPE is essential for ABO-I ***,further research and clinical trials should be conducted to determine the best regimen for TPE to remove ABO antibodies and prevent AMR.

关键词： Plasma exchange ABO blood group system Blood group incompatibility Liver transplantation graft rejection

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

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World Journal of Gastroenterology 2023年第20期29卷 3084-3102页

作者： Hao Wang Zheng-Lu Wang Sai Zhang De-Jun Kong Rui-Ning Yang Lei Cao Jian-Xi Wang Sei Yoshida Zhuo-Lun Song Tao Liu Shun-Li Fan Jia-Shu Ren Jiang-Hong Li Zhong-Yang Shen Hong Zheng The First Central Clinical School Tianjin Medical UniversityTianjin 300190China Department of Organ Transplant Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300190China Key Laboratory of Transplant Medicine Chinese Academy of Medical SciencesTianjin 300190China School of Medicine Nankai UniversityTianjin 300190China Research Institute of Transplant Medicine Nankai UniversityTianjin 300071China Tianjin Key Laboratory for Organ Transplantation Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300071China National Health Commission’s Key Laboratory for Critical Care Medicine Tianjin First Central HospitalTianjin 300071China

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical *** previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy ***,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell ***,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after *** To investigate the functions and underlying mechanisms of antirejection effects of metronomic *** A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after *** vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were *** changes in mitochondrial structure were observed using electron *** With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,Pgraft(7.459 vs 3.432,Prejection after *** vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous *** also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidati

关键词： Capecitabine Ferroptosis T Lymphocytes Immunosuppressive agents graft rejection Liver transplantation

Advances and effectiveness of the immunotherapy after liver transplantation

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World Journal of Gastrointestinal Surgery 2022年第6期14卷 629-631页

作者： Sai Swarupa R Vulasala Nirmal K Onteddu Sindhu P Kumar Chandana Lall Priya Bhosale Mayur K Virarkar Department of Radiology University of Florida College of MedicineJacksonvilleFL 32209United States Department of Internal Medicine Flowers HospitalDothanAL 36305United States Division of Diagnostic Imaging Department of Diagnostic RadiologyThe University of Texas MD Anderson Cancer CenterHoustonTX 77030United States

Transplant recipients usually have increased chances of graft rejection and graft vs host disease,requiring chronic immunosuppressive ***,longterm immunosuppression risks malignancies such as skin cancer,lymphoma,and Kaposi ***,there are very few studies that included solid organ transplant recipients while studying the efficacy of immunotherapy.“Immunotherapy after liver transplantation:Where are we now?”is a study,where the authors described the mechanism of action and outcomes of immune checkpoint inhibitors specific to liver transplant *** authors reported the graft rejection rates and the factors contributing to the rejection in the liver transplant recipients.

关键词： Immunotherapy Hepatocellular carcinoma Immune checkpoint inhibitors Liver transplantation Solid organ transplant graft rejection

Islet transplantation-immunological challenges and current perspectives

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World Journal of Transplantation 2023年第4期13卷 107-121页

作者： Plamena Kabakchieva Yavor Assyov Stavros Gerasoudis Georgi Vasilev Monika Peshevska-Sekulovska Metodija Sekulovski Snezhina Lazova Dimitrina Georgieva Miteva Milena Gulinac Latchezar Tomov Tsvetelina Velikova Clinic of Internal Diseases Naval Hospital-VarnaMilitary Medical AcademyVarna 9010Bulgaria Clinic of Endocrinology Department of Internal DiseasesUniversity Hospital"Alexandrovska"Medical University-SofiaSofia 1434Bulgaria Faculty of Medicine Trakia UniversityStara Zagora 6000Bulgaria Department of Neurology Faculty of MedicineMedical University of PlovdivPlovdiv 4000Bulgaria Department of Gastroenterology University Hospital LozenetzSofia 1407Bulgaria Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Department of Anesthesiology and Intensive Care University hospital LozenetzSofia 1407Bulgaria Department of Pediatric University Hospital"N.I.Pirogov"Sofia 1606Bulgaria Department of Healthcare Faculty of Public Health"Prof.Tsekomir VodenicharovMDDSc"Medical University of SofiaSofia 1527Bulgaria Department of Genetics Sofia University"St.Kliment Ohridski"Sofia 1164Bulgaria Department of General and Clinical Pathology Medical University of PlovdivPlovdiv 4000Bulgaria Department of Informatics New Bulgarian UniversitySofia 1618Bulgaria

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta ***,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay *** review pancreatic islet transplantation as a treatment for T1D and the immunological challenges *** data demonstrated that the time for islet cell transfusion varied between 2 and 10 *** 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second ***,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before *** also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

关键词： Islet transplantation Type 1 diabetes Diabetes mellitus Immune tolerance graft rejection T regulatory cells B regulatory cells

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation

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World Journal of Hepatology 2021年第6期13卷 673-685页

作者： Felicitas Leonie Schotters Jan Beime Andrea Briem-Richter Thomas Binder Uta Herden Enke Freya Grabhorn Department of Pediatric Hepatology and Liver Transplantation Universitätsklinikum Hamburg-EppendorfHamburg 20246Germany Department of Transfusion Medicine Human Leucocyte Antigen LaboratoryUniversity Medicine RostockRostock 18057Germany Department of Hepatobiliary&Transplant Surgery Universitätsklinikum Hamburg-EppendorfHamburg 20246Germany

BACKGROUND In a previous paper,we reported a high prevalence of donor-specific antibody(DSA)in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger *** To clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric *** We performed a retrospective analysis of 123 pediatric liver transplantation(LT)recipients who participated in yearly follow-ups including Luminex testing for DSA at our *** cohort was split into two groups according to the DSA status(DSA-positive n=54,DSA-negative n=69).Groups were compared with regard to liver function,biopsy findings,graft survival,need for re-LT and immunosuppressive *** DSA-positive pediatric patients showed a higher prevalence of chronic rejection(P=0.01),fibrosis(Pgraft *** DQ2,DQ7,DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft *** fluorescence intensity levels and DSA number did not impact graft *** episodes of chronic rejection might lead to DSA *** DSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric *** for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibodymediated rejection improved early identification of patients at risk of graft loss.

关键词： Donor-specific antibodies graft rejection Liver transplantation Fluoroimmunoassay Pediatrics graft dysfunction Fibrosis

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation:A meta-analysis

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World Journal of Gastroenterology 2010年第27期16卷 3457-3464页

作者： Xiang Lan Ming-Man Zhang Cong-Lun Pu Chun-Bao Guo Quan Kang Ying-Chun Li Xiao-Ke Dai Yu-Hua Deng Qiang Xiong Zhi-Mei Ren Department of Hepatobiliary Surgery and Liver Transplantation Centre Children s Hospital of Chongqing Medical University 136 Zhongshan 2nd Road Yuzhong District Chongqing 400014China

AIM:To assess the effect of human leukocyte antigen(HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort ***:Articles in PubMed/MEDLINE,EMBASE and the Cochrane database from January 1970 to June 2009,including non-English literature identified in these databases,were *** studies comparing HLA or sub-phenotype matching with mismatching were *** percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed.A meta-analysis was performed when at least 3 studies provided ***:Sixteen studies met the inclusion criteria.A lower number of HLA mismatches(0-2 vs 3-6) did reduce the incidence of acute rejection(relative risk:0.77,P = 0.03).The degree of HLA mismatching(0-2 vs 3-6) had no significant effect on 1-year [hazard ratio(HR):1.04,P = 0.68] and 5-year(HR:1.09,P = 0.38) graft *** sub-phenotype analysis,the degree of HLA-A,B and DR mismatching(0 vs 1-2) had no significant effect on 1-year and 5-year graft survival,*** HRs and P-values were 0.95,0.71(HLA-A,1-year);1.06,0.60(HLA-A,5-year);0.77,0.16(HLA-B,1-year);1.07,0.56(HLA-DR,1-year);1.18,0.23(HLADR,5-year),***:The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft *** obtain a short recovery time and minimize rejection post transplantation,HLA matching studies should be considered before the operation.

关键词： Human leukocyte antigen Mismatching Liver transplantation Meta-analysis graft rejection

Preoperative single-bolus high-dose antithymocyte globulin as induction therapy in sensitized renal transplant recipients

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Chinese Medical Journal 2006年第20期119卷 1683-1688页

作者： WANG Dong WU Wei-zhen YANG Shun-liang CHEN Jin-hua TAN Jian-ming Department of UrologyFuzhou General Hospitalof PLA Fuzhou 350025 China Department of StatisticsFuzhou General Hospitalof PLA Fuzhou 350025 China

Background Immunological sensitization remains a major problem following renal transplantation. There is no consensus for the management of sensitized renal allograft recipients. The patients become tethered to dialysis while waiting for compatible donors. This study was designed to evaluate the efficacy and safety of preoperative single- bolus high-dose antithymocyte globulin （ATG） as induction therapy in sensitized renal transplant recipients.Methods A total of 56 patients were divided into two groups according to the level of panel reactive antibody （PRA）： non-sensitized group （PRA〈10%, n=30） and sensitized group （PRA≥ 10%, n=26）. The characteristics of the recipients and donors were comparable between the two groups. Mycophenolate mofetil （MMF, 1 g） or ATG （iv. 9 mg/kg） were given preoperatively in the two groups as induction therapy. After the transplantation, the patients were treated with standard triple therapy regimen consisting of tacrolimus （FK-506） or cyclosporine A, MMF, and prednisolone. Acute rejection （AR） and infection episodes were recorded and renal function was monitored during a 12-month follow-up. Х^2 test and t test were used to analyze the data. Results During the follow-up, 6 patients （20.0%） suffered AR episodes in the non-sensitized group and 4 （15.4%） in the sensitized group （P=0.737）; 8 patients （26.7%） experienced 11 infection episodes （average, 1.4 episodes per infected patient） in the non-sensitized group, and 6 （23.1%） experienced 10 infection episodes （average, 1.7 episodes per infected patient） in the sensitized group （P=0.757, 0.890）. The safety of the drugs, which was assessed by the occurrence of side effects, was comparable between the two groups. The hospital stay was 13-25 days （mean, 16.7±3.3） in the non-sensitized group and 14-29 days （mean, 16.2±3.1） in the sensitized group, respectively （P=0.563）. No delayed graft function （DGF） was observed in all the patients. Both the 12-month actuarial patient and graft survival rat

关键词： kidney transplantation graft rejection antilymphocyte serum immunization

Primed macrophages directly and specifically reject allografts

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Cellular & Molecular Immunology 2020年第3期17卷 237-246页

作者： Zhulang Chu Chenming Sun Lina Sun Chang Feng Fan Yang Yanan Xu Yong Zhao State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina

Monocytes and macrophages have long been associated with acute and chronic allograft rejection;this is mediated by their abilities to promote inflammation,kill target cells via antibody-dependent cytotoxicity and modulate adaptive *** present study showed that allogeneic antigen-primed macrophages acutely rejected skin grafts with specificity after adoptive transfer into MHC-matched immunodeficient *** ability of primed macrophages to reject allografts essentially requires the help of CD4^(+) T cells and does not require the help of CD8^(+) T ***,the primed,perforin-deficient macrophages rejected the skin grafts in a significantly delayed pattern compared with WT macrophages,indicating that the perforin pathway of the primed macrophages is likely involved in the rejection ***,primed macrophages are endowed with adaptive immunitylike features,such as specificity,with the help of CD4^(+) T cells during the immune response to *** present study challenges our traditional views of macrophage functions and highlights the biological functions of macrophages beyond innate immunity in mammals.

关键词： Macrophages Specificity graft rejection Innate immunity Transplantation