UBC13对支气管哮喘模型小鼠Th2、Th17型细胞极化的影响

试验旨在探究UBC13蛋白对支气管哮喘小鼠体内Th2、Th17细胞极化的影响。18只BALB/c小鼠随机均分为3组：PBS组、哮喘模型（OVA）组和UBC13蛋白（UBC13）组,OVA组和UBC13组采用卵清蛋白（OVA）和脂多糖（LPS）进行致敏和雾化建立哮喘模型,其中UBC13组于每次雾化前0.5 h腹腔注射100 μg UBC13蛋白。末次雾化激发24 h后处死小鼠,采集样品,通过HE染色观察肺脏切片病理学变化、PAS染色观察气道黏液的分泌,ELISA法检测血清IgE浓度和肺支气管肺泡灌洗液（BALF）上清中IL-4、IL-5和IL-17A的水平,实时荧光定量PCR法检测肺脏Th2型相关因子IL-4、IL-5、IL-13、IFN-γ mRNA和Th17型细胞因子IL-1β、IL-6、IL-17A、IL-23 mRNA的相对表达量。结果显示,试验成功建立了哮喘模型,与PBS组相比,OVA组IgE浓度极显著上升（P < 0.01）,肺脏病理切片炎性细胞浸润和中性黏液分泌现象明显,肺脏中IL-1β、IL-4、IL-6、IL-13和IL-17A mRNA相对表达量均极显著升高（P < 0.01）,IL-5和IL-23 mRNA相对表达量显著升高（P < 0.05）,IFN-γ mRNA相对表达量极显著下降（P < 0.01）,BALF中IL-4、IL-5和IL-17A的水平极显著上升（P < 0.01）;与OVA组相比,UBC13组IgE浓度显著降低（P < 0.05）,病理切片炎性细胞浸润现象减轻、黏液分泌减少,肺脏IL-1β、IL-4、IL-17A、IL-13和IL-23 mRNA相对表达量均显著下降（P < 0.05）,IFN-γ mRNA相对表达量显著升高（P<0.05）;IL-6 mRNA相对表达量极显著下降（P < 0.01）,BALF中IL-5的水平极显著下降（P < 0.01）,IL-4的水平显著下降（P < 0.05）,IL-17A的水平无显著差异（P > 0.05）。由此可见,UBC13蛋白能下调Th2和Th17型细胞因子的表达量,影响哮喘模型Th2和Th17细胞的极化。     

PRRSV感染对细胞自噬与Th1/Th2细胞极化影响的研究进展

猪繁殖与呼吸综合征(PRRS)是一种急性、高度接触性传染病,严重危害着养猪业的健康发展。目前的药物和疫苗不能有效防治该病,因此研究猪繁殖与呼吸综合征病毒(PRRSV)的致病机制具有重要意义。自噬是最新发现的一种细胞维持生存的途径,它是通过降解大分子物质及回收受损细胞来维持细胞内环境稳态变化的一种生理现象,在病原微生物感染过程中发挥关键的调控作用。研究表明,PRRSV感染能够诱导细胞自噬,而自噬参与调控Th1/Th2细胞平衡,Th1/Th2细胞因子极化在宿主防御病原感染中起着至关重要的作用。因此,文章对PRRSV感染、Th1/Th2细胞极化与细胞自噬的相关性,以及Th1/Th2细胞极化与PRRSV的免疫相关性进行综述,以期更加深入地了解PRRSV致病机制。     

糖萜素对小鼠细胞和体液免疫功能的影响

以NIH小鼠为对象,探讨糖萜素对小鼠特异性免疫功能的影响。结果显示:糖萜素饲养组小鼠T细胞增殖作用显著大于对照组(P<0.05);血清IFN-γ和IL-2水平显著高于对照组(P<0.05);脾细胞培养上清IFN-γ水平较对照组显著升高(P<0.05)。此外,糖萜素饲养组小鼠产生的抗体效价及CD4+、CD8+T细胞亚群百分比显著高于对照组(P<0.05)。本研究表明糖萜素能促进小鼠细胞和体液免疫功能。     

肿节风有效成分迷迭香酸对哮喘小鼠Th1/Th2型细胞因子水平的影响

为了探讨肿节风有效成分迷迭香酸对小鼠哮喘模型Th1/Th2细胞因子的调节作用,试验将50只雌性Balb/c小鼠随机分为5组,分别为正常对照组、迷迭香酸单药组、OVA哮喘模型组、迷迭香酸治疗组、地塞米松治疗组,采用ELISA方法对支气管肺泡灌洗液(BALF)中白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-13(IL-13)和γ干扰素(IFN-γ)水平进行了研究。结果表明:与正常对照组比较,OVA哮喘模型组小鼠BALF中IL-4、IL-5和IL-13水平极显著升高(P0.01),IFN-γ水平极显著降低(P0.01),IL-4/IFN-γ比例极显著升高(P0.01);与OVA哮喘模型组比较,迷迭香酸治疗组和地塞米松治疗组显著抑制了IL-4、IL-5和IL-13水平(P0.05),显著降低了IL-4/IFN-γ比值(P0.05)。说明肿节风有效成分迷迭香酸具有抑制哮喘Th2细胞因子和调节免疫平衡的作用。     

TNF-α对IPEC-1细胞生长、屏障功能以及程序性坏死关键基因表达的影响

本试验探讨了肿瘤坏死因子-α(TNF-α)刺激对猪小肠上皮细胞（IPEC-1）细胞生长、屏障功能以及程序性坏死关键基因表达的影响。IPEC-1细胞分别用0或50 ng/mL的TNF-α处理48 h,收集细胞和上清检测相关指标。结果表明：与对照组相比,TNF-α刺激使IPEC-1细胞活力下降（P<0.001）,细胞培养液中乳酸脱氢酶（LDH）活性升高（P<0.05）,细胞数量减少（P<0.05）;TNF-α刺激使IPEC-1细胞跨上皮电阻降低（P<0.05）,同时荧光素异硫氰酸酯-葡聚糖4(FD4)通透性增加（P<0.05）;TNF-α刺激使咬合蛋白（Occludin）和闭合小环蛋白-1(ZO-1)的膜分布紊乱,Occludin(P<0.001)和ZO-1(P<0.05)的表达量降低;TNF-α刺激增加了程序性坏死关键因子受体相互作用蛋白激酶3(RIP3)和混合系激酶样结构域蛋白（MLKL）的mRNA表达量（P<0.05）。以上结果表明,TNF-α刺激诱导IPEC-1细胞损伤,破坏了细胞屏障,激活了细胞程序性坏死信号通路。     

产细胞毒性坏死因子2型牛大肠杆菌血清型

测定了１０１株从粪便中分离的产细胞毒性坏死因子２型（ＣＮＦ２）的牛产坏死毒素大肠杆菌（ＮＴＥＣ）的血清型，虽然产生ＣＮＦ２的ＮＴＥＣ属于４８种不同Ｏ：Ｋ：Ｈ血清型，但其中１１种血清型占测定菌株的５４％，按频率排列，最普通的血清型是：Ｏ１２３：Ｋ－：Ｈ１６；Ｏ３：Ｋ－：Ｈ２１；Ｏ８８：Ｋ－：Ｈ８；Ｏ１５：Ｋ１４：Ｈ２１；Ｏ１：Ｋ－：Ｈ１２；Ｏ１：Ｋ１：Ｈ４６；Ｏ２；Ｋ１：Ｈ５；Ｏ５５；Ｈ２１；Ｏ８８     

复方中草药制剂对Th1／Th2细胞平衡的调节

针对威胁人类安全及动物生产的慢性疾病、病毒性疾病、癌症等疑难杂症，中医药学结合Th1／Th2细胞平衡理论开展了许多临床及实验研究，并已取得了一定的成果。本文在综述前人研究成果基础上，提出了深入探讨Th1／Th2细胞平衡与中医阴阳学说内在的关系和加强中草药免疫药理学机理研究的必要性。同时，以中草药复方制剂对疾病免疫平衡调节的研究为突破口，很可能是攻克众多疑难杂症的主要途径。     

新疆野生荒漠肉苁蓉醇提物调节小鼠DCs成熟对Th1/Th2的免疫增强作用

旨在探讨新疆野生荒漠肉苁蓉醇提物(ethanol extracts of wild Cistanche deserticola,EEWCD)调节Th1/Th2免疫反应的特点及初步的作用机制.采用卵清白蛋白(ovalbumin,OVA)为抗原,研究EEWCD对小鼠体液免疫,细胞免疫,细胞因子分泌,树突状细胞(dendri...     

尾蚴抗原特异性的T细胞克隆的建立及其功能测定:Ⅰ.T细胞克隆的建立

本文报道了用早期感染曼氏血吸虫的C57BL/6小鼠纵隔淋巴结细胞建立七株对血吸虫尾拗抗原特异性的T细胞克隆,其中两株在被动免疫转移试验中对血吸虫的攻击感染具有显著的保护作用。用荧光标记的单克隆抗体检测证明七株T细胞克隆均为Thyl.2~+、 L_3T_4~+、 Lyt2~-的T辅助细胞。     

Th1/Th2 balance in canine peripheral blood lymphocytes--a flow cytometric study

The canine immune system undergoes continuous remodeling with advancing age. We measured the Th1/Th2 balance in peripheral blood lymphocytes (PBLs) obtained from 23 Beagles ranging in age from 0.5 to 11.8 years by flow cytometric analysis using intracellular cytokine staining. The percentage of CD4 cells producing interferon-gamma (Th1) increased with age. The percentage of CD4 cells producing interleukin-4 (Th2) increased but much less so. In conclusion, we demonstrated that the Th1/Th2 balance in canine peripheral blood could be measured by this flow cytometry technique and the Th1/Th2 balance inclined to dominance of the Th1 subpopulation in PBLs as the dog matured.     

Th1/Th2 polarization by viral and helminth infection in birds

Mammals developed an immune system able to functionally polarize into so-called type 1 or type 2 immune pathways, to resolve infections with intracellular and extracellular pathogens, respectively. In the well-studied avian immune system of the chicken, however, no evidence for polarized immunity could be found, as yet. To investigate whether these two major arms of mammalian immunity, regulated by a T helper (Th)1/Th2 cytokine balance, evolved similarly in birds, chickens were exposed to a prevalent intracellular (viral) or extracellular (helminth) infection. By using semi-quantitative RT-PCR analysis we provide evidence that polarization of Th1/Th2 type immunity extends beyond mammalian species, and, therefore, has been evolutionary conserved for more than 300 million years, when the lineages of mammalian and avian vertebrates are assumed to have segregated.     

Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance

Immune imbalance of Treg/Th17 cells may contribute to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). In this study, we sought to determine the effect of intrauterine administration of mouse PBMCs prior to embryo implantation on endometrial receptivity and embryo implantation, and examine the underlying mechanism of Treg/Th17 cell balance following intrauterine administration of PBMCs. Pregnant mice were randomly divided into three groups: control group, embryo implantation dysfunction (EID) group, and EID with PBMCs group, and the number of embryo implantation sites was recorded during early pregnancy (Pd7.5). The balance of Treg/Th17 cells in the peripheral blood, spleen, and local implantation sites was detected during the peri-implantation period (Pd4.0) and early pregnancy (Pd7.5). The EID group demonstrated a significant decrease in the number of embryo implantation sites, while the EID with PBMCs group demonstrated higher number of embryo implantation sites compared to the EID group. The balance of Treg/Th17 cells in the peripheral blood and spleen tissues was not significantly different between the aforementioned groups. However, the local uterine ratio of the Treg/Th17 cells increased in the EID with PBMCs group compared to that in the EID group. Collectively, we found that intrauterine administration of PBMCs prior to embryo implantation effectively promotes embryo implantation rates. This may be attributed to the improvement in the local immune balance of Treg and Th17 cells compared with the overall immune balance.     

Th1/Th2型细胞因子的动态变化对山羊妊娠的影响

为了研究Th1/Th2型细胞因子的动态变化对山羊妊娠的影响,探讨其生理学意义,试验通过EUSA方法对山羊妊娠早期及流产前后外周血液中Th1(TNF-α、IL-2)与Th2(IL-10)型细胞因子的含量进行了检测.结果表明:妊娠早期外周血液中TNF-α和IL-2含量先升高后降低,IL-10含量持续上升;流产后TNF-α和IL-2含量高于流产前含量(P＜0.01或P＜0.05),IL-10则低于流产前含量(P＜0.05或P＜0.01).说明山羊正常妊娠时Th1/Th2型细胞因子动态平衡应当是以Th2型免疫及其相关因子占优势,平衡失调则导致妊娠失败.     

PRRSV感染对猪外周血来源的树突状细胞免疫表型及Th1/Th2偏转潜能的影响

为了研究PRRSV感染对猪外周血来源的树突状细胞成熟及Thl及Th2型细胞因子分泌水平的影响,进一步探讨PRRSV调控树状细胞Th1和Th2型免疫应答的潜在机制,揭示PRRSV感染对机体免疫机能的影响。我们从猪外周血分离单核细胞,诱导培养为树突状细胞后接种PRRSV共培养,显微镜观察细胞的形态,流式细胞术分析细胞表面的共刺激分子,半定量RT-PCR法检测Thl型细胞因子IL-12和Th2型细胞因子IL-10的mRNA转录水平。结果显示:经鉴定证实获得形态及表型典型的树突状细胞;流式分析结果表明PRRSV接种组树突状细胞表面的SLA-II-DR类分子、CD40分子、CD80分子均明显低于未接种组,差异极显著(P0.01);RT-PCR半定量结果表明PRRSV接种组的IL-12mRNA转录水平低于未接种组,差异显著(P0.05),而IL-10mRNA转录水平高于未接种组,差异显著(P0.05)。结果表明:PRRSV感染影响树突状细胞的成熟,并能通过高效表达Th2型细胞因子IL-10降低Th2型细胞因子Th1而影响Thl/Th2的平衡。     

Effect of plasma transfusion on neutrophil function in healthy and septic foals

OBJECTIVE: To evaluate the effect of plasma transfusion on phagocytosis and oxidative burst activity of peripheral blood neutrophils from healthy and septic equine neonates with sub-optimal passive transfer of maternal immunity. ANIMALS: Nine healthy and seven septic foals with suboptimal passive transfer of maternal immunity (serum IgG < 8 g/L) presented to participating veterinary hospitals for plasma transfusion, and seven healthy foals less than 7 days of age and with circulating IgG concentrations > or = 8 g/L. PROCEDURE: Foals with serum IgG concentrations < 8 g/L were assessed as healthy or septic. Sepsis was recognised by positive bacterial cultures and/or sepsis scores of > or = 11. All foals received between 1 and 3 L of plasma to boost circulating IgG concentrations to > or = 8 g/L. Serum IgG concentrations were determined before and following transfusion by glutaraldehyde coagulation test and confirmed by single radial immunodiffusion assays. Neutrophil phagocytosis and oxidative burst activity were determined before plasma transfusion and at 0 h, 12 h, 24 h, 48 h and 5 d following treatment. Neutrophil function from seven healthy foals less than 7 d of age and with circulating IgG concentrations of > or = 8 g/L was similarly evaluated on a single occasion. RESULTS: Plasma treatment significantly increased circulating IgG concentrations for healthy and septic foals. Oxidative burst activity of neutrophils from septic foals was significantly increased 5 days following treatment, relative to 0 h post treatment. Other differences were not significant but suggested a transient decrease in phagocytosis by neutrophils from healthy foals and increased phagocytosis by neutrophils from septic foals immediately following transfusion. Oxidative burst activity of neutrophils from septic foals tended to be less than that of healthy foals at all sampling times. Serum IgG concentrations were not correlated with neutrophil phagocytosis, but were correlated with oxidative burst activity. CONCLUSIONS: Plasma transfusion did not improve neutrophil function of healthy foals, suggesting that such treatment may be of equivocal benefit for healthy neonates. Conversely, improved neutrophil function was observed following treatment of septic foals, suggesting that plasma transfusion was beneficial for these foals. Oxidative burst activity of neutrophils from septic foals was lower than that of neutrophils from healthy foals and was significantly improved 5 days post treatment, when compared with values obtained immediately following treatment.     

Influence of transfusion technique on survival of autologous red blood cells in the dog

Objective – To determine the effect of 3 differing transfusion techniques on survival of autologous canine RBCs. Design – Prospective, blinded study. Setting – University Teaching Hospital. Animals – Nine healthy dogs. Interventions – Three distinct preparations of RBCs, each representing ～1% of red cell mass, were generated for each dog by biotinylation of RBCs at varying biotin densities. Labeled cells were transfused using 3 techniques (gravity, volumetric pump, syringe pump). Serial determinations of red cell survival were carried out by flow‐cytometric analysis of RBCs collected at 7‐day intervals for 49 days. In vitro analysis of the effect of transfusion methods on RBC integrity and osmotic fragility were carried out in 7/9 dogs. Measurements and Main Results – RBCs administered via volumetric and syringe pumps exhibited a marked decrease in short‐term probability of survival compared with RBCs delivered by gravity flow. At 24 hours, only 4/8 and 1/7 dogs had surviving cell populations delivered by volumetric and syringe pump, respectively, compared with 8/8 dogs which had surviving cell populations delivered by gravity flow. Circulating half‐life of cells surviving at 24 hours after delivery by volumetric pump was not significantly different to that delivered by gravity flow. No significant effect on in vitro RBC integrity or osmotic fragility was detected in relation to transfusion technique. Conclusions – Delivery of autologous canine RBCs via mechanical delivery systems was associated with a high risk for early loss of transfused cells.     

妊娠期激素对Th1和Th2细胞因子的调控

妊娠是一个复杂的生理过程,受到神经、免疫和内分泌的共同调节。作为半自体抗原的胎儿不被母体排斥是子宫局部免疫水平调节的结果。其中激素对辅助性淋巴细胞(Th)发生、分化的调节作用愈来愈受到重视。辅助T淋巴细胞能分化为不同的亚型(Th1和Th2),孕酮可促进Th2型细胞因子(IL-4,IL-5)的产生,有利于妊娠的正常发生;松弛肽促进Th1型细胞因子(IFN-γ)的产生,对妊娠有害。在母胎界面存在激素-细胞因子网络,淋巴细胞产生的细胞因子还能够影响其他细胞因子的产生。由Th2样细胞产生的,对胚泡着床具有非常重要作用的白血病抑制因子(LIF),其表达受Th1细胞诱导因子的下调,如IL-12,IFN-α,IFN-γ,受IL-4和孕酮(诱导T淋巴细胞向Th2细胞分化)的上调。激素通过调控淋巴细胞分泌的细胞因子来调控免疫系统,保持一个动态的平衡,有利于维持妊娠。     

Increased Th1/Th2 (IFN-gamma/IL-4) Cytokine mRNA ratio of rat embryos in the pregnant mouse uterus

Somatic cell nuclei can be dedifferentiated in ooplasm from another species, and interspecies cloned embryos can be implanted into the uteri of surrogates. However, no full pregnancies have been achieved through interspecific mammalian cloning. Rat blastocysts transferred into mouse uteri provide a unique model for studying the causes of interspecific pregnancy failure. In this study, intraspecific pregnancy (mouse-mouse) and interspecific pregnancy (rat-mouse) models were established. On Day 9 of pregnancy, the fetoplacental units were separated from the uterine implantation sites and the expression of messenger (m)RNA was quantitated by real-time PCR. We compared the mRNA expression levels of type-1 T helper (Th1) and type-2 T helper (Th2) cytokines, interferon-gamma (IFN-gamma), and interleukin-4 (IL-4) in fetoplacental units between intraspecific and interspecific pregnancy groups. The mRNA expression of IFN-gamma in the fetoplacental units of the interspecific pregnancy group was significantly higher than that of the intraspecific pregnancy group (P<0.05). The mRNA expression of IL-4 in the interspecific pregnancy group was significantly lower than that in the intraspecific pregnancy group (P<0.05). We also analyzed the ratio of IFN-gamma/IL-4 mRNA, and an increased IFN-gamma/IL-4 mRNA ratio was observed in the interspecific pregnancy compared with that in the intraspecific pregnancy group. The IFN-gamma and IL-4 mRNA expressions indicate that there is a Th1/Th2 imbalance in the feto-maternal interface of interspecific pregnancies. Bias of Th1 cytokine dominance may be a barrier to reproductive success between species.