移植免疫耐受的研究进展

诱导对移植物的特异性耐受是解决器官移植中排斥反应的理想方法之一,本文综述了器官移植中免疫耐受的机制及诱导和维持免疫耐受的方法。     

免疫耐受的研究进展

免疫耐受是器官移植领域中重要课题。本文各种免疫耐受现象、机理、诱导方法和临床应用情况进行简述。     

免疫耐受的现状与展望

半个世纪以来,免疫学逐步发展成为了一门关于研究自我和非自我接受与排斥的科学。大量的实验与临床观察表明,正常免疫系统总会以种种机制将具有非自我遗传特性的移植物摧毁。如何让正常个体长期接受一个非自我的器官移植物而又不以牺牲机体的耐受力为代价,这就是本文将...     

免疫耐受与移植

本文概述了通过主动诱导、阻断免疫应答和建立白细胞微嵌合体诱导耐受的最新进展。细胞毒性T细胞相关抗原4(CTLA4)可通过阻断共刺激使T细胞无能,诱导耐受。IL-4和IL-10是T辅助细胞(Th)2细胞因子,能诱使免疫向Th2方向偏离,促进耐受形成;IL-10也是细胞因子合成抑制因子,可通过抑制宿主抗原提呈细胞抑制免疫。重点阐述了CTLA4和IL-4、IL-10的作用机制和研究现状,各种诱导方法的联合应用及其在异种移植中的具体实施。在用CTLA4成功诱导同种异体骨移植耐受的基础上,探讨了异种骨移植的特点,以及通过诱导免疫耐受防止异种骨移植排斥的可行性。     

甲状旁腺移植免疫耐受实验研究

本文主要研究以SD大鼠作供体,以Wistar大鼠为受体的甲状旁腺移植免疫耐受的实验。通过本实验研究揭示移植前输注供体肝细胞可诱导免疫耐受产生;而输注适当剂量的肝细胞免疫抗原,对移植物的存活期长短有重要作用。CsA可明显改善器官移植的存活期;它在抗原暴露前应用可抑制受体T细胞的活性,使受体的免疫系统对移植物产生耐受性。供体肝细胞输注及CsA联合使用,本组无1例动物达到长期存活,这可能与加用CsA后干扰体内免疫调节机能有关。     

移植免疫耐受研究进展

皮肤移植是覆盖烧伤创面的重要手段 ,成功的皮肤移植对烧伤感染、休克的预防及创面愈合、愈后生活质量都至关重要。但自体皮源在烧伤后往往不足且自体皮的获取本身对机体就是一种损伤 ,因此异基因 (异体、异种 )皮肤移植仍是烧伤创面覆盖的重要措施之一。要达到理想的移植效果     

调节性T细胞在移植免疫耐受中的研究进展

诱导移植免疫耐受需产生免疫反应下调。多年来,被称为抑制性T细胞现被命名为调节性T细胞(regulatory T cells,Treg),Treg在免疫应答的负性调控中发挥着重要作用。Treg介导的连锁性抑制和传染性耐受解释了发挥免疫耐受的机制。Treg通过离体扩增后回输体内,有望成为移植免疫耐受新的免疫过继疗法。     

树突状细胞与移植免疫耐受

树突状细胞 (ＤＣ)是目前已知功能最强的专职抗原递呈细胞。它最大的特点是捕获外来抗原 ,迁移至引流淋巴结 ,发育成熟并递呈抗原 ,启动和诱导Ｔ细胞分化产生免疫反应或直接激活Ｂ细胞及产生免疫记忆[1] ,因此ＤＣ是免疫应答的始动者。本文就近两年ＤＣ与免疫耐受的关系作一综述。一、树突状细胞亚群ＤＣ是一异质的细胞群体 ,其异质性主要表现在不同的细胞起源、不同的成熟状态和功能方面[2 ] 。细胞起源和成熟程度差异决定着ＤＣ的不同功能 ,这与免疫耐受诱导有着十分密切的关系。根据ＤＣ表面蛋白质分子 ,可将源于小鼠骨髓和胸腺或淋巴器…     

大鼠脾移植诱导特异性免疫耐受效果

目的 比较异位脾移植和原位脾移植诱导特异性免疫耐受的效果.方法 建立大鼠异位脾移植和原位脾移植模型6周后,二期行同源心脏移植,比较移植心脏的存活时间和移植5d后的排斥反应强度.以单纯心脏移植组和心脏移植+环孢菌素组作为对照组.结果 移植心脏存活时间:心脏移植+环孢菌素组＞原位脾移植组＞异位脾移植组＞单纯心脏移植组(P＜0.05).术后第7天排斥反应强度和混合淋巴细胞反应强度测定:心脏移植+环孢菌素组＜原位脾移植组＜异位脾移植组＜单纯心脏移植组(P＜0.05).结论 由于脾脏的生理功能与门静脉系统的回流特点有关,较之于异位脾移植,原位脾移植能更为有效地诱导受体特异性免疫耐受状态.     

基因转移技术在诱导移植免疫耐受中的应用策略

近年来器官移植已经取得重要进展，移植前的组织配型、供体的预处理以及移植部位的选择等手段明显减轻了移植免疫排斥反应，各种免疫制剂的长期应用进一步控制了排斥反应。但由于无关人群中，HLA相同的个体十分罕见，而免疫抑制目前的方法有许多明显的副作用，慢性移植排斥也没     

Tolerance induction in clinical transplantation

Introduction of modern immunosuppressive agents has led to great success of allotransplantation in humans, and survival rates for all solid organs have been dramatically improved. However, a constant proportion of organs is lost every year due to chronic allograft rejection and immunosuppressive drug toxicity. This has led to a situation where, despite the of donor organ shortage, about one third of the patients on the kidney transplant waiting list are listed for a retransplant. The induction of donor-specific tolerance has the potential of at least partially resolving this problem, since it might prevent chronic rejection and drug toxicity at the same time. For a variety of protocols, successful tolerance induction has been demonstrated in rodent models. However, translation of such protocols to large animal models and on clinical trials has turned out to be very difficult. This review briefly describes mechanisms and barriers to transplantation tolerance, and then focuses on pre-clinical and clinical studies in non-human primates and humans. We have divided the strategies into two groups, based on the principle mechanisms of tolerance induction: the first group are protocols not using hematopoietic stem cell transplantation (HCT) as part of there regimen. They rely mainly on intensive T cell depletion (either by total body irradiation, total lymphoid irradiation or treatment with T cell-depleting agents such as anti-thymocyte globulin, anti-CD52 antibody or CD3 immunotoxin), which have been combined with costimulatory blockade, signaling blockade or donor antigen infusion. The second group are HCT-based protocols combining HCT with T cell-depleting agents and cytoreductive treatment. So far, only two protocols (one with total lymphoid irradiation and anti-thymocyte globulin, but no HCT; one with HCT, cyclophosphamide, anti-thymocyte globulin and thymic irradiation) have been translated into successful human studies. We summarize and discuss the results of these trials and suggest goals for further studies for the development tolerance protocols applicable for a broad population of allograft recipients.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

目的 观察小鼠Sertoli细胞是否能在异体内起到诱导局部免疫耐受、保护共移植异体胰岛的作用.方法 以糖尿病C57小鼠作移植受体,随机分4组,每组6只;以正常BALB/C小鼠为胰岛供体,正常C57小鼠和正常BALB/C小鼠各作为Serloli细胞供体.A组:单纯移植异体胰岛;B组:移植来源于C57小鼠的Sertoli细胞+BALB/C小鼠来源的胰岛;C组:移植均来源于BALB/C小鼠的Sertoli细胞及胰岛;D组:假手术组.监测各组移植受体的血糖尿糖变化,观察移植物的存活时间.结果 A组移植物平均存活时间为(6.50±2.35)d;B组为(55.67±4.84)d;C组为(51.33±5.05)d;D组未观察到血糖正常.B组及C组的移植方式均可逆转糖尿病小鼠的高血糖状态,移植物存活期均较A组有明显延长,其差异有统计学意义(P<0.05);而B组与C组的移植物存活时间差异无统计学意义(P>0.05).结论 同种异体来源的睾丸Sertoli细胞在异体内可起到诱导局部免疫耐受的效果,对共移植同种异体胰岛起到保护作用,其效果与自体睾丸Sertoli细胞相当.     

小鼠异体Sertoli细胞诱导胰岛移植免疫耐受的作用

Objective To study whether the sertoli cell allograft can achieve the immunotolerance and protect the co-transplant islet allograft on the heterotopic situation. Methods The diabetic C57 mice were used as recipients, and healthy BALB/C mice as islet donors,respectively. Healthy BALB/C and C57 mice were used as testis sertoli cell donors. The recipients were randomly divided into 4 groups,6 mice in each group : group A: only transplant with islet allograft;group B: co-transplant with islet allograft and serto-li isograft;group C:co-transplant with islet allograft and sertoli allograft;group D:sham-operated group. The blood and urine glucose levels in the models, and the survival time of the graft were observed. Results The mean survive time of graft in groups A, B, and C was (6.50±2.35 ), (55.67±4.84), and (51.33± 5.05 ) days respectively. In group D, blood glucose level was abnormal. The hyperglycemia of the diabetic C57 mice could be reversed by the transplant methods of groups B and C. The mean survival time in groups B and C was longer than in group A P < 0.05, but there was no significant differences between groups B and C,P > 0.05. Conclusion The sertoli cells can induce local immunotolerance and protect the co-transplant islet allograft. Sertoli cell isograft can obtain the same local immunotolerance as the sertoli cell allograft.