细胞免疫在不同纲(罗非鱼/大鼠)肝细胞移植排斥反应中的作用

目的 探讨罗非鱼到大鼠肝细胞移植的细胞免疫排斥反应机制.方法 SD 大鼠随机分为移植组和对照组,实验组脾内移植2伊107 个罗非鱼肝细胞,对照组脾内注射生理盐水.术后以HE 染色法观察移植物组织学变化,SABC 免疫组化法检测移植物周围大鼠CD4、CD8 阳性细胞.结果 肝移植术后2 h 罗非鱼肝细胞形态完整,4 h出现部分肝细胞边界不清,核固缩、溶解,8 h 后很难见到正常肝细胞.移植后4 h 移植物周围可见CD4 和CD8 阳性细胞聚集.结论 在罗非鱼肝细胞移植到大鼠脾内诱发的排斥反应中,细胞免疫可能具有重要作用.     

细胞外基质在移植肾慢性排斥反应中的作用

细胞外基质在移植肾慢性排斥反应中的作用郭颖，郭琳琅移植肾慢性排斥反应是由细胞免疫和体液免疫参与的复杂免疫反应过程，最终导致肾小球和血管硬化，引起移植肾功能严重损害。我们应用免疫组化方法和计算机图象分析系统，旨在通过对慢性排斥反应移植肾细胞外基质中Ⅳ型...     

细胞毒性蛋白检测在移植肝急性排斥反应诊断中的意义

目的检测移植肝组织中穿孔素、颗粒酶B及细胞毒颗粒相关蛋白（TIA-1）的表达情况，评价其在肝移植术后急性排斥反应诊断及鉴别诊断中的意义。方法应用免疫组织化学方法检测肝移植术后急性排斥组和非排斥组患者移植肝组织中穿孔素、颗粒酶B及TIA-1的表达情况；结合组织形态学观察，分析肝组织中不同区域的阳性细胞数量。结果肝移植术后共行移植肝组织活检108例次，其中排斥组62例次，非排斥组46例次。两组移植肝汇管区及小叶内表达穿孔素、颗粒酶B及TIA-1的阳性细胞数比较，差异均有统计学意义（P〈0．05）；两组移植肝胆管或血管中表达阳性的细胞浸润率比较，差异也有统计学意义（P〈0．05）。表达穿孔素和颗粒酶B的阳性细胞数与排斥反应组织学分级及肝功能生化指标（天冬氨酸转氨酶和γ-谷酰转肽酶）升高成正相关。结论检测移植肝组织中穿孔素、颗粒酶B及TIA-1的表达对急性排斥反应的诊断及分级具有重要意义。     

肾移植排斥反应移植物中基因表达的研究

移植肾急性排斥是同种异体肾脏移植主要的临床问题，是慢性移植肾失功能的主要危险因素。监测血清肌酐水平、应用免疫组织化学方法或病理检查来诊断急性排斥、预测慢性排斥的发生不是很敏感，也不是很可靠。目前，人们应用分子生物学的技术方法来研究试验动物移植物和临床病理组织标本中与排斥有关的基因及其表达产物来筛选标志性基因，有望对肾移植排斥反应做出早期诊断并预测其发生，进而为阐明移植物排斥的机理以及基因治疗指明方向。     

肾移植排斥反应移植物中基因表达的研究

移植肾急性排斥是同种异体肾脏移植主要的临床问题 ,是慢性移植肾失功能的主要危险因素。监测血清肌酐水平、应用免疫组织化学方法或病理检查来诊断急性排斥、预测慢性排斥的发生不是很敏感 ,也不是很可靠。目前 ,人们应用分子生物学的技术方法来研究试验动物移植物和临床病理组织标本中与排斥有关的基因及其表达产物来筛选标志性基因 ,有望对肾移植排斥反应做出早期诊断并预测其发生 ,进而为阐明移植物排斥的机理以及基因治疗指明方向     

免疫活化基因与急性排斥反应

免疫活化基因在免疫细胞活化增殖和发挥效应的过程中，同时或相继表达并介导重要的生理功能，在一定程度上预示免疫反应的程度和转归，并对不同研究结果进行了初步分析。     

MICA分子及其在肾移植排斥反应中的作用

MICA分子是非经典的HLA-I类基因MICA编码的膜结合蛋白,为应激诱生性抗原,具高度多态性,主要表达于上皮细胞、血管内皮细胞和成纤维细胞的表面.MICA分子不但与某些肿瘤、感染及自身免疫性疾病相关,而且可能在肾移植的排斥反应中发挥重要作用.MICA通过与其受体NKG2D的特异性结合而启动体液免疫和细胞免疫,参与移植肾的急慢性排斥反应,导致移植物失功.     

Fas介导细胞凋亡通路在慢性排斥反应所致移植物血管病变中的作用

目的 通过建立小鼠心脏及主动脉移植模型探讨Fas途径介导细胞凋亡在慢性排斥反应所致移植物血管病变形成中的作用。方法 (1)正常B6及B6．MRL(Fas-／-)→B10．2R小鼠腹腔异位心脏移植。B10．2R→B6小鼠胸主动脉异位移植。定期获取移植物。观察移植物存活率与组织形态学改变；TUNEL及FITC Annexin V／PI双染色方法检测移植物中凋亡细胞形态及分布；B6小鼠主动脉体外培养。人重组的可溶性FasL诱导平滑肌细胞凋亡。结果 B6．MRL(Fas-／-)供体来源移植物存活期显著延长，其血管平滑肌细胞凋亡明显减少。新生血管内膜中的平滑肌细胞具有抗Fas介导凋亡的特性。结论 在慢性排斥反应所致移植物血管病变形成中Fas途径及平滑肌细胞对Fas介导凋亡的敏感性具有重要作用。     

FTY720在鼠类异种胰岛移植排斥反应中的作用

目的 在小鼠异种胰岛细胞移植模型上，研究FTY720在控制异种胰岛移植排斥反应中的作用。方法 使用胰管内胶原酶注射和不连续密度梯度纯化法获取大鼠胰岛，建立小鼠肾被膜下移植模型。受体小鼠随机分为3组：对照组，末使用任何免疫抑制药物；实验1组，自移植当日起每日单独喂服FTY720(1.0mg／kg)；实验2组，亦于移植当日起每日联合喂服FTY720(1.0mg／kg)和环孢霉素A(CsA，15mg／kg)，均连续喂饲14d。分别于术后第3，5，7，14天切取移植物，观察并分析排斥反应。结果 对照组和实验1组，植入。肾被膜下的胰岛组织多在1周内完全被排斥，术后第7天胰岛轮廓消失，仅见大量淋巴细胞浸润。实验2组于移植后第7天及第14天肾被膜下仍可见大量完整的胰岛细胞，几乎未见或偶尔可见淋巴细咆浸润。结论 FTY720单独作为免疫抑制剂并不能抑制鼠类异种胰岛移植的排斥反应；联合应用FTY720及CsA则可有效地抑制鼠类异种胰岛移植排斥反应的发生。     

免疫活化基因与急性排斥反应

免疫活化基因在免疫细胞活化增殖和发挥效应的过程中 ,同时或相继表达并介导重要的生理功能 ,在一定程度上预示免疫反应的程度和转归 ,并对不同研究结果进行了初步分析。     

Acute humoral renal allograft rejection

In kidney transplantation, it is well established that donor-specific antibodies can cause substantial graft injury. Hyperacute rejection, now virtually eliminated by routine pretransplant cytotoxic crossmatch testing, represents the prototype of humoral rejection. However, there is now increasing evidence that alloantibody-mediated immune reactions may also cause acute rejection. Acute humoral rejection, which is frequently associated with severe graft dysfunction and immunologic graft loss, represents a particular diagnostic and therapeutic challenge. Reliable detection of antibody-mediated graft injury is required to govern the application of antihumoral therapeutic strategies. This review focuses on new approaches in the diagnosis and treatment of acute humoral rejection. Special attention is given to a novel diagnostic marker, the complement split product C4d.     

Antibody-mediated renal allograft rejection: diagnosis and pathogenesis

Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection and accommodation.     

Antibody-mediated rejection

The introduction of both complement 4d (C4d) staining in renal allograft biopsies and sensitive methods to detect anti-human leukocyte antigen antibodies, such as single antigen bead flow assays, into tissue-typing techniques have shown the importance of antibody-mediated alloimmune response in kidney transplantation. The use of these sensitive methods, combined with the increased number of transplants in highly sensitized patients with donor-specific antibodies, or patients receiving desensitization protocols, have increased the awareness and thus the incidence of acute antibody-mediated rejection. Chronic rejection also can be mediated through alloantibodies, and the term chronic antibody-mediated rejection recently was proposed. In this review article we summarize the current knowledge of the role of alloantibodies in transplantation, the diagnosis and treatment of acute and chronic antibody-mediated rejection, and their effect on graft function and outcome.     

Antibody-mediated kidney allograft rejection: therapeutic options and their experimental rationale

With the advent of novel therapies to directly intervene with B cell immunity and complement activation, antibody-mediated kidney allograft rejection (AMR) has come into the focus of transplant immunologists. Intravenous immunoglobulin, rituximab, bortezomib, and eculizumab have been used to treat patients with acute AMR, apart from the standard treatment of antibody removal with plasma exchange or immunoadsorption and steroid pulses. This article describes the experimental rationale and summarizes the still limited clinical experience with these novel therapies in the transplant setting. Results with the standard treatment for acute AMR, including intense plasmapheresis, intravenous immunoglobulins, and steroids are good with a graft survival of 80% at 18 months. In contrast, patients suffering from chronic AMR have significant irreversible damage in their grafts with substantially impaired graft survival. Thus, the authors propose a step-wise escalation of therapy in refractory cases of acute AMR and advocate an urgent need for controlled therapeutic trials for acute and chronic AMR not to inflict unnecessary harm on our patients by uncontrolled polypragmasy.     

急性体液性排斥反应对移植肾预后的影响

Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.     

急性体液性排斥反应对移植肾预后的影响

Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.