T cell antigenicity and immunogenicity of allogeneic exosomes

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.     

Clinical use of donation after circulatory death pancreas for islet transplantation

Due to a shortage of donation after brain death (DBD) organs, donation after circulatory death (DCD) is increasingly performed. In the field of islet transplantation, there is uncertainty regarding the suitability of DCD pancreas in terms of islet yield and function after islet isolation. The aim of this study was to investigate the potential use of DCD pancreas for islet transplantation. Islet isolation procedures from 126 category 3 DCD and 258 DBD pancreas were performed in a 9-year period. Islet yield after isolation was significantly lower for DCD compared to DBD pancreas (395 515 islet equivalents [IEQ] and 480 017 IEQ, respectively; p = .003). The decrease in IEQ during 2 days of culture was not different between the two groups. Warm ischemia time was not related to DCD islet yield. In vitro insulin secretion after a glucose challenge was similar between DCD and DBD islets. After islet transplantation, DCD islet graft recipients had similar graft function (AUC C-peptide) during mixed meal tolerance tests and Igls score compared to DBD graft recipients. In conclusion, DCD islets can be considered for clinical islet transplantation.     

The natural killer cell activating receptor,NKG2D,is critical to antibody-dependent chronic rejection in heart transplantation

Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag^−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease.     

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.     

基于慢性乙型病毒性肝炎诊断路径的实验诊断学教学模式初探

探讨建立涵盖慢性乙型病毒性肝炎(CHB)诊断与鉴别诊断、治疗、药物选择及毒副作用预测、疗效监测、预后评估等全过程的疾病临床检验诊断路径的教学模式。根据CHB临床诊疗指南, 制订与疾病不同阶段相关的实验室检查检测策略, 建立CHB临床检验诊断路径, 以武汉大学第一临床学院2016级和2017级八年制本科生为研究对象, 通过随堂问卷比较其课堂教学效果。本研究首先建立了获得临床医生认可的CHB临床检验诊断路径, 其涵盖CHB疾病的诊断与鉴别诊断、治疗、药物选择及毒副作用预测、疗效监测、预后评估等全过程。该路径应用于2017级临床医学本科生课堂教学后, 教学质量评估指标均有较大程度的提升。此外, 随堂测验得分也有显著提高。综上, 基于CHB临床检验诊断路径的实验诊断学教学模式, 实现了实验诊断学与临床医学的融合, 提升了学生对CHB诊疗中各种实验室检查检测的整体认识, 教学质量得到了提高。     

粉防己碱对兔瘢痕组织作用的实验研究

目的 :研究粉防己碱对兔病理性瘢痕的组织学作用 ,为瘢痕治疗提供一种新方法。方法 :采用兔耳腹侧瘢痕模型 ,用粉防己碱 5 0mg /ml、粉防己碱 10mg /ml、去炎松 40mg /ml及生理盐水分别注入瘢痕组织 ,图像分析瘢痕组织中成纤维细胞数量和胶原含量的变化。结果 :粉防己碱治疗组瘢痕组织中成纤维细胞数量与胶原含量均明显减少 ,呈剂量效应关系 ;与生理盐水对照组比较 ,有极显著差异 (P <0 .0 1) ;与去炎松对照组比较无显著差别 (P >0 .0 5 )。结论 :粉防己碱抑制瘢痕组织中成纤维细胞增殖 ,并使胶原合成减少 ,从而抑制瘢痕组织生长 ,有望成为防治病理性瘢痕的新药物     

国产全热解碳双叶瓣的动物实验

目的 :探讨人造瓣膜动物实验的方法 ,并对国产瓣的性能作动物体内评价。方法 :体外循环下行羊的二尖瓣替换术 ,先作预实验以确定实验方法 ,后作正式实验。用心导管和超声 ,并用多巴酚丁胺负荷法模拟运动条件 ,分别测定人造瓣的血流动力学参数 ;根据动物存活情况及有无血栓形成和血栓栓塞等评价其生物相容性。结果 :预实验 10只羊均死亡 ,主要与瓣环撕裂有关 ;正式实验 5只羊均存活。术中和术后 2 .5年用导管法测得平均跨瓣压差分别为 0 .69± 0 .2 3k Pa、0 .81± 0 .0 4k Pa;动物尸检未见血栓形成和血栓栓塞。结论 :瓣环撕裂是本组手术主要死亡原因 ,选择适当体重的动物和保留瓣叶的折叠缝补 ,及术后合理的呼吸支持等是实验的关键 ;该国产瓣在动物体内血流动力学和抗血栓性能优良     

顺行和逆行取栓对静脉瓣膜及血管壁的影响

目的：比较顺行取栓与逆行取栓在猪腋静脉急性血栓形成对于其瓣膜功能和静脉壁形态的影响。方法：分别结扎猪的腋静脉的近远端,于结扎段内注入凝血酶原,放置６ｈ使形成血栓。随机分配为顺行取栓和逆行取栓组,对血栓段进行取栓。取栓后２４ｈ行取栓静脉插管逆行造影以评估瓣膜功能;切取此段静脉作ＣＤ８＾＋细胞免疫组化和苏木精－伊红（ＨＥ）染色以对比血管内膜及平滑肌的损伤程度。结果：逆行与顺行取栓在所有的例数中都成功地