乳腺癌患者B7-CD28共刺激通路的研究

目的探讨乳腺癌患者外周血中CD2 8表达阳性的T细胞数量和患者乳腺癌原代细胞表面B7 1(CD80 )、B7 2 (CD86 )的表达水平 ,以探讨乳腺癌患者共刺激通路是否异常。方法采用流式细胞技术检测乳腺癌患者外周血中CD2 8阳性T细胞与乳腺癌患者原代细胞B7分子的表达 ,并与乳腺良性疾病作比较。结果乳腺癌患者CD2 8阳性的T细胞数明显低于对照组 (t =2 879,P <0 0 5 ) ,特别是CD4/CD2 8双阳性T细胞数更低于对照组 (t=3 0 17,P <0 0 0 1)。乳腺癌患者原代细胞表面B7 1和B7 2表达水平都低于对照组。结论乳腺癌患者外周血中T细胞低表达CD2 8分子 ,乳腺癌细胞低表达B7分子 ,从而影响B7 CD2 8共刺激通路 ,使T细胞不能有效地清除肿瘤细胞。     

环孢素对共刺激阻断剂延长移植肾存活效应的影响

目的:探讨环孢素(CsA)对共刺激阻断剂CTLA4Ig延长移植肾存活效应的影响。方法:肾移植大鼠分为对照组(第1组)、CTLA4Ig组(第2组)、CsA CTLA4Ig组(第3组)、CTLA4Ig IL-2组(第4组)和CsA CTLA4Ig IL-2组(第5组),观察术后血肌酐(Scr)、移植肾病理改变、移植肾存活时间。结果:与第1组、第4组相比,第2组、第3组、第5组移植肾存活时间显著延长(P<0.01),其中,第3组移植肾存活时间最长(66.1±10.6)d;术后15天,第2组Scr显著低于第3组、第5组(P<0.05);术后30天,第3组、第5组Scr显著低于第2组(P<0.01);术后30天,第3组、第5组移植肾淋巴细胞浸润明显少于第2组。结论:CsA可增强CTLA4Ig延长移植肾存活的效应,对外源性IL-2逆转CTLA4Ig的效应具有抵抗作用。     

共刺激信号阻断剂基因局部转染对大鼠移植肾存活的影响

目的　观察CTLA 4Ig基因局部转染延长移植肾存活的效能。 方法　以CTLA 4Ig基因重组腺病毒为载体 ,将CTLA 4Ig基因转入BN大鼠肾脏。以BN大鼠为供者 ,Lewis大鼠为受者 ,行同种肾移植术。用经CTLA 4Ig基因转染的供肾移植给受者为转染组 ;用未转染CTLA 4Ig基因的供肾移植给受者为对照组。观察移植肾存活时间和术后肾功能变化。结果　转染组移植肾存活 (32± 8.0 )d ,对照组移植肾存活 (8.5± 1.4 )d ,转染组存活时间明显延长 ;转染组术后血清肌酐较同期对照组明显为低。结论　CTLA 4Ig基因局部转染供肾可明显延长移植肾的存活时间。     

B7-CD28/CTLA4共刺激通路与胰岛移植

目的：探讨B7-CD28/细胞毒T淋巴细胞相关蛋白4(CTLA4)共刺激通路在胰岛移植中的重要作用。方法：采用文献回顾的方法对该共刺激通路的分子结构、功能以及有关动物实验的资料进行综述。结果：B7-CD28/CT-LA4共刺激通路是T淋巴细胞活化、增殖的信号传导通路之一，若缺乏共刺激信号，则会导致T淋巴细胞呈克隆无反应状态。CTLA4-Ig通过阻断CD28介导的共刺激通路，使胰岛移植物在受者体内长期存活。结论：通过对B7-CD28/CT-LA4共刺激通路的研究，有助于了解移植胰岛存活的免疫机理。     

CD28／CTLA4—B7T细胞共刺激通路与移植免疫

在Ｔ细胞介导的免疫应答过程中，共刺激通路是Ｔ细胞活化，增殖的必备条件。近年来在器官移植的实验中发现，通过阻断Ｔ细胞共刺激通路可以使移植物存活时间明显延长，甚至长期存活。因此，通过此途径胡否诱导出受体对供体特异的免疫耐受状态已成为移植免疫研究的新热点。     

靶向B7/CD28共刺激信号系统防治移植物抗宿主病的新策略

移植物抗宿主病 (ＧＶＨＤ)已成为临床异体造血干细胞移植 (ＨＳＣＴ)面临的最大障碍之一 ,如何改善或克服现有免疫抑制剂或方法存在的弊端 ,抑或创造出新一代理想、高效、特异、低毒、能防治或减弱ＧＶＨＤ的新策略或措施 ,已成为迫切需要解决的问题 ,这也是当今异体造血干细胞移植与移植免疫学研究领域的中心课题。现已证实 ,无论是对于免疫耐受的诱导 ,还是在ＧＶＨＤ的防治方面 ,Ｂ7:ＣＤ2 8/Ｔ淋巴细胞相关抗原 4(ＣＴＬＡ4 )共刺激信号系统均极为重要 ,正成为当今异体造血干细胞移植、器官移植、移植免疫和相关新型免疫抑制剂创新性开…     

CTLA4Ig基因和CD40Ig基因转染供肾对异种大鼠移植肾存活的影响

目的 探讨细胞毒性T淋巴细胞相关抗原4融合蛋白(CTLA4Ig)基因和CD40Ig基因转染供肾对异种大鼠移植肾存活的影响.方法 以PcDNA3.1质粒为载体,通过脂质体2000将CTLA4Ig基因和CD40Ig基因转染豚鼠肾脏,再移植(异位肾移植)给SD大鼠.实验分4组进行:第1组供肾以PcDNA3.1空载体脂质体复合物转染(空载体组);第2组供肾转染CD40Ig基因(CD40Ig转染组);第3组供肾转染CTLA4Ig基因(CTLA4Ig转染组);第4组供肾同时转染CTLA4Ig基因和CD40Ig基因(双基因转染组).术后观察各组血清肌酐、移植肾组织病理改变以及移植肾存活时间.结果 空载体组、CD40Ig转染组、CTLA4Ig转染组和双基因转染组受者的存活时间分别为(6.8±1.9)d、(40.7±10.9)d、(49.3±9.5)d和(75.7±8.0)d,3个转染组明显长于空载体组(P＜0.01),其中双基因转染组移植肾存活时间最长,与其他3组比较,差异均有统计学意义(P＜0.01).各组术后血清肌酐水平呈上升趋势,但升高幅度以双基因转染组为最低(P＜0.01).术后第30天,CD40Ig转染组和CTLA4Ig转染组存活大鼠的移植肾组织中可见大量淋巴细胞浸润,而双基因转染组的移植肾组织中仅见少量淋巴细胞浸润.结论 供肾局部同时转染CTLA4Ig基因和CD40Ig基因可明显延长其异种移植后的存活时间.     

新型衍生肽对淋巴细胞免疫功能及大鼠异基因移植肾存活的影响

目的 探讨新型组织相容性白细胞抗原（HLA）衍生肽RDPI258对淋巴细胞免疫功能及大鼠移植肾脏存活时间的影响。方法 采用人工标准固相合成法合成HLA衍生肽RDP1258，^3H—TdR掺入法观察其在体外对人外周单核细胞增殖反应的影响。建立原位大鼠异基因肾移植模型32只，设RDP1258＋CsA治疗组、RDP1258治疗组、CsA治疗组及对照组4组，每组8只，观察大鼠移植肾脏存活时间及移植肾功能。结果RDP1258可显著抑制淋巴细胞转化及单向混合淋巴细胞增殖反应（MLR）；RDP1258＋CsA治疗组受体大鼠平均存活63．4d，对照组平均存活9．4d，CsA治疗组平均存活16．9d，RDP1258治疗组平均18．3d，各组与联合治疗组比较差异有统计学意义（P〈0．05）。对照组在术后5d切除对侧肾脏后血清肌酐浓度（450．0±84．2）μmol／L，CsA及RDP1258组血清肌酐浓度呈现缓慢上升趋势，分别为（360．0±78．4）及（350．0±65．8）μmol／L，与联合治疗组（47．4±11．2）μmol／L相比，差异有统计学意义（P〈0．05）。结论 RDP258能显著抑制人外周单核细胞丝裂原或同种抗原刺激引起的增殖反应，围手术期应用HLAⅠ类分子衍生肽结合小剂量CsA，能显著延长异基因移植物存活时间及功能，RDP1258可能成为一种新型的器官移植免疫调节药物。     

急性细胞性排斥反应时移植肾组织中B7-1及相关蛋白的表达

Ｂ7/ＣＤ2 8双信号刺激途经在排斥反应、肿瘤、自身免疫性疾病中的作用倍受重视。我们对 4 2例移植肾组织中Ｂ7 1及相关蛋白的表达进行了研究 ,旨在探讨Ｂ7 1分子在急性细胞性排斥反应时的表达。一、材料与方法1.材料来源 :4 2份移植肾标本分为3组 :10例正常供肾组织为对照组 ;10例移植肾功能稳定者为正常组 ;2 2例急性细胞性排斥反应组织为排斥组。2 .诊断标准 :急性细胞性排斥反应的诊断依据临床表现、实验室检查、病理穿刺活检等 ,并排除其它原因造成的移植肾功能异常。3.试剂和实验方法 :(1)试剂 :抗Ｂ7 1单克隆抗体由我校生命科学院免…     

表达IκBα突变体的树突状细胞对大鼠移植肾存活时间的影响

目的 观察IκBα突变体基因修饰的供体树突状细胞(IκBαM-Dc)对大鼠移植肾存活时间的影响.方法 利用重组腺病毒载体将IκBαM基因转染WF大鼠骨髓DC,流式细胞仪检测DC共刺激分子CD80、CD86表达.以wF大鼠为供体,Lewis大鼠为受体,行同种肾移植.术前7 d,受体输注供体IκBαM-DC作为IκBαM组,未输注IκBαM-DC的受体作为对照组,观察移植肾存活时间和术后肾功能变化.术后第14天检测受体T细胞对供体成熟DC及第三方大鼠成熟DC的反应性.结果 IκBαM明显抑制DC共刺激分子CD80、CD86表达.IκBαM组受体鼠移植肾存活时间为(32.5±7.8)d,较对照组移植肾存活时间(8.5±1.7)d明显延长(P<0.01);而其术后7 d血清肌酐为(57.3±8.2)μmol/L,较对照组血清肌酐(498.0±46.3)μmol/L明显减低.肾移植术后,IκBαM组受体T细胞对供体成熟DC反应明显低于对照组,而对第三方大鼠成熟DC的反应性与对照组比较,差异无统计学意义(P>0.05).结论 表达IκBα突变体的供体树突状细胞能诱导受体大鼠T细胞对供体抗原的免疫低反应,显著延长大鼠移植肾存活时间.     

阻断B7诱导大鼠心脏移植免疫耐受的实验研究

目的　研究阻断B7方法诱导大鼠心脏异位移植的免疫耐受。　方法　采用Ono法建立大鼠异位心脏移植模型 ,实验组腹腔注射B7阻断剂CTLA 4Ig,观察大鼠移植的心脏存活天数 ,病理改变和术后IL 2 ,IgG以及IgM含量的变化。　结果　实验组移植的心脏存活时间为 :(31 6 0± 1 82 )d ,对照组 (7 2 5± 0 71)d ,差异有显著性意义 (P <0 0 1)。组织学改变 :实验组见局灶性血管周围或间质内淋巴细胞浸润和局灶性心肌损伤 ,病理分级Ⅰ～Ⅱ级。对照组可见大量淋巴细胞浸润 ,心肌细胞损伤和坏死 ,间质内出血水肿 ,病理分级Ⅳ级。术后IL 2含量实验组比对照组明显下降 ,有显著性差异 ,P <0 0 1。IgG和IgM含量差异无显著性意义 (P >0 0 5 )。　结论　阻断B7能诱导大鼠心脏移植免疫耐受 ,为移植排斥反应提供了新的治疗方法     

Effect of the shipment of cadaveric renal allografts on allograft survival.

BACKGROUND: Since 1996, the allocation of grafts in France has been based on a hierarchical three-level system: national, regional and local. The objective of this study was to determine whether the shipment of cadaveric kidneys according to these new exchange rules affects allograft outcome in the Eastern region of France. METHODS: This retrospective study analysed all renal transplants performed in the four centres of the French Eastern region during 3 years (1996 to 1998). All patients were followed up until death, return to dialysis, last information date or the end of June 2003. Information regarding the donors, recipients and treatments, as well as patient and graft outcome, was recorded. Factors associated with graft loss were analysed using Cox proportional hazard methods. RESULTS: 542 transplants were analysed, 287 (53%) kidneys were transplanted locally, 229 (42.2%) kidneys coming from exchanges within the region and 26 (4.8%) from another region. There were statistically significant differences between the four centres for donors' and recipient' characteristics and for immunosuppressive treatment, but there was no difference between centres regarding patient survival (94.4% at 5 years), graft survival (83.7% at 5 years) or death-censored graft survival (87.8% at 5 years). Compared to locally transplanted grafts, shipped grafts had significantly better human leukocyte antigen (HLA) matching (2.5 +/- 1.3 versus 2.1 +/- 1.0 matches, P = 0.0005 but a longer cold ischaemia time (23.2 +/- 7.9 versus 19.2 +/- 7.8 h, P < 0.0001). Three independent factors were associated with a reduced graft survival: at least one acute rejection, delayed graft function and a shipped graft. CONCLUSION: The results of this study suggest that the shipment of cadaveric renal allografts in a regional distribution system is associated with better HLA matching but is a significant predictor of graft loss at 5 years. It would be advisable to restrict graft sharing to patients whose access to transplantation is limited, taking special care to avoid any additional factors having a detrimental effect on the outcome.     

Peripheral donor leukocytes prolong survival of rat renal allografts.

BACKGROUND: The development of strategies to enhance the survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advancement in post-transplant patient care. METHODS: We studied the effect of pretransplant infusion of donor leukocytes alone or in combination with a short course of cyclosporine on the long-term outcome of a rat model of kidney allograft. RESULTS: A single intravenous infusion of donor peripheral blood leukocytes (100x10(6) cells) from Brown-Norway (BN) rats into major histocompatibility complex (MHC) incompatible Lewis recipients largely failed to prolong kidney allograft viability from the same donor transplanted 60, 40, or 30 days after cell infusion. A short course of cyclosporine (per se, unable to prolong graft survival) was started at the same day of donor leukocyte infusion, but instead was able to prolong the survival of the BN kidney transplant-performed 40 days later-but not of a Wistar Furth (WF) third party, with some animals even developing tolerance. A mixed lymphocyte reaction of host cells from long-term surviving rats to BN stimulator cells was significantly reduced as compared with controls. Donor BN DNA was detected in the peripheral blood of Lewis rats until day 40 after BN leukocyte infusion. Microchimerism persisted (60 to 70 days post-transplant) in most long-term graft recipients. Reducing the time interval between donor leukocyte infusion and subsequent kidney transplant to 10 days still prolonged graft survival. Donor peripheral blood mononuclear cells, but not polymorphonuclear cells, in the leukocyte preparation contributed to prolong kidney allograft survival. CONCLUSIONS: Pretransplant donor leukocyte infusion under the appropriate conditions can tip the immune balance toward improved graft acceptance. This result could be relevant to the achievement of donor-specific tolerance of the graft with the maintenance of an intact response to third-party antigens.