小鼠胸腺内注射异基因抗原对异体神经移植免疫反应的影响

目的　探讨胸腺内注射异基因抗原对异体鼠坐骨神经移植存活的影响。　方法　 70只Balb/c小鼠随机分为 5组 :自体神经移植组 (A组 )、异体神经移植组 (B组 )、冷冻后异体神经移植组 (C组 )、应用免疫抑制剂异体神经移植组 (D组 )和胸腺内注射供体组织相容性 (MHC)抗原后移植组 (E组 )。 3周后进行神经电生理检查、组织学检查、混合淋巴细胞培养及迟发性超敏反应的检测。　结果　运动神经传导速度E组为 3 8 2 3 (m /s) ,与D组相比差异无显著性 (P >0 0 5 ) ,且E组优于C组、B组。混合淋巴细胞培养E组为 2 668 3 7(cpm ) ,迟发性超敏反应E组为 0 5 10 (cpm ) ,组织学及电镜检查均证实A组优于E组、E组分别优于C组、D组、B组。　结论　胸腺内注射异基因抗原可诱导对异体坐骨神经移植的特异性免疫耐受。     

胰十二指肠切除术对胰头癌患者CD4~+CD25~+调节性T细胞的影响及临床意义

目的研究胰头癌患者外周血中CD4+CD25+调节性T细胞(Treg)比例及其在手术前、后的变化趋势。方法采用流式细胞仪检测胰头癌患者及正常对照组外周血中CD4+CD25+调节性T细胞的数量,同时监测CD4+/CD8+比值,并进行手术前、后的比较。结果胰头癌患者术前外周血中CD4+CD25+和CD4+CD25highTreg所占比例较正常对照组高(P<0.05),术后则出现不同程度下降,以术后第3天下降最明显(P<0.01,P<0.05);胰头癌患者术后CA19-9水平低于术前,以术后第14天下降明显(P<0.05)。CD4+CD25highTreg与CA19-9的变化趋势大致相同。胰头癌患者术前CD4+/CD8+比值比正常对照组低(P<0.05),手术后进一步降低,于手术后第7天达最低(P<0.05)。结论胰十二指肠切除术可能有助于机体抗肿瘤免疫的恢复,胰头癌患者围手术期可作为免疫干预的重要窗口期,CD4+CD25+调节性T细胞可作为免疫干预的靶点。     

Galectin-9基因转染诱导大鼠肾移植免疫耐受的实验研究

[目的]探讨半乳凝素-9(Galectin-9)在大鼠肾移植免疫耐受中的作用及意义。[方法]建立大鼠同种肾移植模型,分为Lentiviral-Galectin-9组、雷帕霉素组、对照组和Lentiviral组。lentiviral-Galectin-9组供肾移植前用含慢病毒lentiviral-Galectin-9的肾脏冷保存液经肾动脉灌注。分别观察肾功能测定、生存期,检测尿蛋白和血肌酐含量,移植肾病理检查并半定量评分,比较各组间的不同。[结果]Lentiviral-Galectin-9治疗组肾移植受体大鼠平均存活天数为30.2d,与对照组的存活时间比较差异显著。Lentiviral-Galectin-9治疗组的移植肾功能基本保持稳定。脾细胞增殖反应显示:Lentiviral-Galectin-9组和雷帕霉素组对供体脾细胞的刺激增殖反应显著低于对照组和Lentiviral组,Lentivi-ral-Galectin-9组对供体脾细胞的刺激增殖反应显著低于和雷帕霉素组,差异均有统计学意义。Lentiviral-Galectin-9组和雷帕霉素组的尿蛋白水平明显低于对照组和Lentiviral组,差异均有统计学意义(P﹤0.05);Lentiviral-Galectin-9组与雷帕霉素组差异有统计学意义(P﹤0.05),对照组和Lentiviral组差异无统计学意义(P﹥0.05)。第6周和第12周时,Lentiviral-Galectin-9组和雷帕霉素组的血肌酐浓度明显低于对照组和Lentiviral组,差异均有统计学意义(P﹤0.05);Lentiviral-Galectin-9组与雷帕霉素组差异有统计学意义(P﹤0.05),对照组和Lentiviral组差异无统计学意义(P﹥0.05)。移植术后12周时,Lentiviral-Galectin-9组和雷帕霉素组大鼠移植肾组织的间质炎症和纤维化、血管内膜增厚、肾小球硬化和小管萎缩等慢性损害明显轻于对照组和Lentiviral组,Lentiviral-Galectin-9组损害轻于雷帕霉素组,差异均有统计学意义(P﹤0.05);对照组和Lentiviral组差异无统计学意义(P﹥0.05)。[结论]慢病毒lentiviral载体可成功介导Galectin-9基因对大鼠肾脏的转染,并对移植肾起免疫保护作用、延长移植肾的存活时间。     

诱导新生小鼠对Graves病免疫耐受的研究

目的 研究TSH受体(TSHR)289基因诱导Graves病新生免疫耐受的可行性,并初步探索其可能机制.方法 将出生0～24hBALB/c雌性小鼠分为腹腔注射组、肌肉注射组、造模组及正常对照组,腹腔注射组或肌肉注射组分别设低剂量、中剂量、高剂量耐受组及相应对照组,将腹腔注射、肌肉注射不同剂量耐受组及各自对照组给予1×106particles(低)、1×108particles(中)、1×1010particles(高)的Ad-TSHR289或Ad-lacz进行预处理6～7周后,除正常对照组肌肉注射Ad-lacz外,其余各组小鼠均给予Ad-TSHR289免疫,每3周1次,共3次,首次免疫后10d检测血清促甲状腺素受体抗体(TRAb),末次免疫后4周测血清TRAb、TT4、脾CD4+CD25+Foxp3/CD4+比例,并行甲状腺组织学检查.结果 首次注射后10d,腹腔注射及肌肉注射高剂量耐受组均未诱导出针对TSHR的抗体反应,而对照组TRAb滴度明显升高(P＜0.05).末次免疫后4周,腹腔及肌肉注射高剂量耐受组均只有1/10小鼠出现阳性的抗体反应,腹腔注射高剂量耐受组没有小鼠发生甲状腺功能亢进,而肌肉注射高剂耐受量组2/10小鼠出现轻微的TT4升高,其相应对照组却出现了强烈的抗体反应(P＜0.01),TT4水平明显升高(P＜0.05),所有TT4升高的小鼠均出现了甲状腺组织增生性改变.此外,腹腔注射及肌肉注射高剂量耐受组CD4+CD25+Foxp3/CD4+比例与对照组比较明显增高(P＜0.01)腹腔注射及肌肉注射其余组群,与其对照组和造模组比较Graves病发生率差异无统计学意义.结论 TSHR 289基因可以通过腺病毒为载体,腹腔和肌肉注射两种途径诱导新生小鼠成年后对Graves病免疫耐受,抑制Graves病的发生.而高剂量的抗原刺激容易导致耐受产生.CD4+CD25+Foxp3+T细胞在免疫耐受的诱导和维持中可能起重要作用.     

胰十二指肠切除术对胰头癌患者CD4^＋CD25^＋调节性T细胞的影响及临床意义

目的研究胰头癌患者外周血中CD4^＋CD25^＋调节性T细胞（Treg）比例及其在手术前、后的变化趋势。方法采用流式细胞仪检测胰头癌患者及正常对照组外周血中CD4^＋CD25^＋调节性T细胞的数量,同时监测CD4^＋/CD8^＋比值,并进行手术前、后的比较。结果胰头癌患者术前外周血中CD4^＋CD25^＋和CD4＋CD25highTreg所占比例较正常对照组高（P〈0.05）,术后则出现不同程度下降,以术后第3天下降最明显（P〈0.01,P〈0.05）;胰头癌患者术后CA19-9水平低于术前,以术后第14天下降明显（P〈0.05）。CD4＋CD25highTreg与CA19-9的变化趋势大致相同。胰头癌患者术前CD4^＋/CD8^＋比值比正常对照组低（P〈0.05）,手术后进一步降低,于手术后第7天达最低（P〈0.05）。结论胰十二指肠切除术可能有助于机体抗肿瘤免疫的恢复,胰头癌患者围手术期可作为免疫干预的重要窗口期,CD4^＋CD25^＋调节性T细胞可作为免疫干预的靶点。     

卫生假说的免疫学机制在哮喘防治中的研究进展

哮喘的特征是慢性气道炎症和气道高反应性。目前对哮喘治疗的认识是“可以控制,但不能治愈”。近年来,哮喘发病的“卫生假说”提出早期微生物的暴露可能对哮喘的发病起保护作用。传统的解释是微生物负荷增加可诱导免疫反应向Th1偏移。由于哮喘是由免疫耐受缺陷导致的疾病,因此诱导抗原特异性T细胞耐受可能是此假说的另一种解释,并有望因此为防治哮喘提供新的思路。     

Fas/FasL与支气管哮喘

Fas受体和Fas配体(FasL)在免疫细胞上的表达相对较高,其介导的细胞凋亡、增殖与免疫细胞的凋亡、增殖及功能发挥密切相关,在哮喘免疫耐受及调控异常、Th1/Th2失衡、气道炎症、黏液产生、气道高反应及气道重塑中发挥了重要作用,有望成为哮喘治疗的突破口。但是,在Fas/FasL信号转导过程中,各种因素构成了一个复杂的调控网络,深入研究Fas/FasL信号转导途径及其相关的调控机制才能为哮喘治疗开创新途径。     

Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in liver transplantation

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.     

丁酸钠诱导的未成熟树突状细胞的免疫学功能研究

目的： 探讨丁酸钠对人外周血来源的树突状细胞（DC）的成熟状态和免疫学功能的影响。方法： 通过粒细胞－巨噬细胞集落刺激因子（GM-CSF）和白细胞介素4（IL-4）结合丁酸钠体外诱导人外周血来源的DC，6 d后结合不同成熟因子诱导成熟，并以流式细胞仪、FITC标记的Dextran的内吞检测、混合淋巴细胞反应（MLR）、ELISA法分别检测DC的表面标志、内吞能力、DC刺激淋巴细胞增殖能力和白细胞介素12（IL-12）分泌量的改变。结果： 丁酸钠可以抑制DC成熟，使DC具有较强的抗原吞噬能力，而刺激淋巴细胞增殖能力和IL-12的分泌能力下降。结论： 丁酸钠可以抑制DC成熟，诱导不成熟DC生成，在移植免疫耐受方面具有较好的应用前景。     

Recombinant Pregnancy-Specific Glycoprotein 1 Has a Protective Role in a Murine Model of Acute Graft-versus-Host Disease

Acute graft-versus-host disease (aGVHD) is an immune-mediated reaction that can occur after hematopoietic stem cell transplantation in which donor T cells recognize the host antigens as foreign, destroying host tissues. Establishment of a tolerogenic immune environment while preserving the immune response to infectious agents is required for successful bone marrow transplantation. Pregnancy-specific glycoprotein 1 (PSG1), which is secreted by the human placenta into the maternal circulation throughout pregnancy, likely plays a role in maintaining immunotolerance to prevent rejection of the fetus by the maternal immune system. We have previously shown that PSG1 activates the latent form of transforming growth factor β1 (TGF-β), a cytokine essential for the differentiation of tolerance-inducing CD4⁺FoxP3⁺ regulatory T cells (Tregs). Consistent with this observation, treatment of naïve murine T cells with PSG1 resulted in a significant increase in FoxP3⁺ cells that was blocked by a TGF-β receptor I inhibitor. We also show here that PSG1 can increase the availability of active TGF-β in vivo. As the role of CD4⁺FoxP3⁺ cells in the prevention of aGVHD is well established, we tested whether PSG1 has beneficial effects in a murine aGHVD transplantation model. PSG1-treated mice had reduced numbers of tissue-infiltrating inflammatory CD3⁺ T cells and had increased expression of FoxP3 in T cells compared with vehicle-treated mice. In addition, administration of PSG1 significantly inhibited aGVHD-associated weight loss and mortality. On the other hand, administration of PSG1 was less effective in managing aGVHD in the presence of an alloimmune reaction against a malignancy in a graft-versus-leukemia experimental model. Combined, this data strongly suggests that PSG1 could be a promising treatment option for patients with aGVHD following bone marrow transplantation for a nonmalignant condition, such as an autoimmune disorder or a genetic immunodeficiency.