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Adjuvant effects of different TLR agonists on the induction of allergen-specific Th2 responses

open journal of Immunology 2012年第1期2卷 17-24页

作者： Matthias j. Duechs james E. brunt Florian gantner Klaus j. Erb Respiratory Diseases Research Boehringer Ingelheim Pharma GmbH & Co. KG biberach an der Riss Germany

Currently different Toll-like receptor (TLR) agonists are tested in humans for their ability to enhance the efficacy of specific immunotherapy (SIT). Recent clinical data suggest that this may be achieved by increasing allergen-specific Th1 responses. however, it is not clear which TLR agonist is best suited to be used in combination with SIT. we tested the ability of five TLR agonists, LTA, poly(I:C), LPS, R848, and Cpg-oDN, activating TLR2, 3, 4, 7, and 9, to induce allergen-specific Th1 and suppress allergen-specific Th2 responses in a preclinical setting. Mice were immunized by intraperitoneal injection of ovalbumin (ova)/Al(oh)3 together with different doses (0.0025, 0.025, 0.25, and 2.5 mg/kg) of agonists followed by two ova aerosol challenges. The results of these experiments showed, that the suppression of allergen-specific Th2 responses and the induction of Th1 responses dependedon the dose and the agonists used. All TLR agonists increased allergen-specific Igg2a, and with the exception of poly(I:C), reduced allergen-specific IgE levels in the serum. Allergic cutaneous anaphylaxis was also suppressed in mice when LPS or Cpg was given together with ova/alum. The strongest Th1 responses were induced by Cpg and poly(I:C), characterized by the presence of IFN-g in the bAL and the highest ova-specific Igg2a levels in the serum. This study suggests that the TLR9 agonist Cpg-oDN and TLR4 agonist LPS have the strongest suppressive effects on the development of aller-gen-specific Th2 responses in mice and Cpg-oDN induces the strongest allergen-specific Th1 responses. Therefore these two TLR agonists may be good candidates to combine with allergen in novel SIT formulations in humans.

关键词： Asthma TLR-agonists Innate-Inflammation Inhibition

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CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma

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Chinese Medical journal 2006年第23期119卷 1983-1990页

作者： wANg hui-ying ShEN hua-hao james j Lee Nancy A Lee Department of Respiratory Medicine Second Affiliated Hospital ofZhejiang University Medical College Institute of RespiratoryDiseases of Zhejiang University Hangzhou 310009 China Department of biochemistry and Molecular biology Mayo ClinicScottsdale Scottsdale Arizona 85259 USA

background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AhR） and pathological changes （inflammatory cells infiltration and mucus production）. Eosinophils play a key role in the allergic inflammation. but the causative relationship between eosinophils and airway inflammation is hard to prove. one of the reasons is lack of activation marker of murine eosinophils. we investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. Methods Eosinophils from peripheral blood of IL-5 transgenic mice （Nj.1638） were purified. Mice were divided into five groups： wild type mice sensitized and challenged with saline （wS group）, wild type mice sensitized and challenged with ovalbumin （wo group）, IL-5^-/- mice sensitized and challenged with saline and transferred with purified eosinophils （ISE group）, IL-5^-/- mice sensitized and challenged with ova and transferred with purified eosinophils （IoE group）, IL-5^-/- mice sensitized and challenged with ova and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody （IoE＋antiCD4mAb group）. IL-5^-/- mice were sensitized with ova at day 0 and day 14, then challenged with ova aerosol. on days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5^-/- mice. on day 28, blood and bALF were collected and CD69 expression on eosinophils measured by flowcytometry. Results Purified eosinophils did not express CD69. but eosinophils cultured with PMA＋MA, IFN- T, IL-5 or gM-CSF expressed CD69 strongly. Eosinophils from blood of wo, wS group did not express CD69 at all. The numbers of eosinophils in bALF of wo group, IoE group, ISE group and IoE＋antiCD4mAb group were significantly higher than in mice of wS group which did not have eosinophils at all. CD69

关键词： asthma eosinophils CD69 airway inflammation murine model

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Substance Pantagonist improves both obesity and asthma in a mouse model

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世界最新医学信息文摘 2014年第7期 7-7页

作者： R.Ramalho j.Almeida M.beltr?o A.Pirraco R.Costa o.Sokhatska L.guard?o C.Palmares j.T.guimar?es L.Delgado A.Moreira R.Soares

background Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain *** P (SP), involved in neurogenic inflammation by acting through its receptor NK1-R, seems to participate in obeseasthma phenotype in *** To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet-induced obesity and ***-induced obese balb/c mice were sensitized and challenged with ovalbumin (ova) and treated with a selective NK1-Rantagonist or placebo. Serum glucose, insulin, IL-6, resistin, and ova-specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were *** ovalbumin-obese mice treated with NK1-R antagonist had lower weight (P = 0.0002), reduced daily food intake (P = 0.0021),reduced daily energy intake (P = 0.0021), reduced surface adipocyte areas (P ower serum glucose (P = 0.04), lowerserum insulin (P = 0.03), lower serum IL-(P = 0.0022), lower serum resistin (P = 0.0043), lower serum ova specific IgE (P =0.035), and lower peribronchial inflammation score (P han nontreated ova-obese mice. we observed an interaction between obesity, allergen sensitization, and treatment with NK1-R antagonist for metabolic and systemic biomarkers, and forallergen sensitization and bronchial inflammation, showing a synergy between these *** & Clinical Relevance In an experimental model of obesity and asthma in mice, NK1-R blockade improved metabolic and systemic biomarkers, as wellas allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese–asthma phenotype and highlight SP as a target with potential clinical interest in the obese–asthma epidemics.

关键词： ova Substance Pantagonist improves both obesity and asthma in a mouse model

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以兔抗鼠淋巴细胞血清为非条件刺激的条件性免疫抑制

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心理学报 2002年第3期34卷 295-300页

作者：林文娟陈极寰 A.j.husband 中国科学院心理研究所脑-行为研究中心北京100101 DepartmentofVeterinaryPathology

采用一种生物类免疫抑制剂—兔抗鼠淋巴血清 (rabbitanti ratlymphocyteserum ,ALS)为非条件刺激(UCS)、糖精水为条件刺激 (CS) ,以双瓶给水法置于鼠笼前端饮用偏好侧。在一次性CS—UCS结合训练后 ,单独再次给予CS ,使卵清蛋白 (ova)免... 详细信息

采用一种生物类免疫抑制剂—兔抗鼠淋巴血清 (rabbitanti ratlymphocyteserum ,ALS)为非条件刺激(UCS)、糖精水为条件刺激 (CS) ,以双瓶给水法置于鼠笼前端饮用偏好侧。在一次性CS—UCS结合训练后 ,单独再次给予CS ,使卵清蛋白 (ova)免疫过的大鼠表现出脾淋巴细胞对有丝分裂原PwM的增殖反应降低、血抗ova抗体的总量及脾内抗ova抗体生成细胞的减少。但动物未表现出条件性味觉厌恶的行为反应。这些结果表明条件性免疫抑制与味觉厌恶性行为条件反射没有必然联系 ,并非是厌恶行为反应或情绪应激的伴随产物 ,UCS也并非必需具有感觉的毒副作用。

关键词：兔抗鼠淋巴细胞血清味觉厌恶条件刺激条件反射性免疫抑制大鼠

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T_h细胞在记忆性CTL介导的肿瘤抑制中的作用研究

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中华微生物学和免疫学杂志 2005年第4期25卷 286-291页

作者：高丰光 germain j. P. Fernando 刘文军厦门大学医学院免疫学教研室 361005 entre for Immunology and Cancer Research University of Queensland Princess Alexandra Hospital Brisbane QLD4102 Australia Clinical Medical Virology Centre University of Queensland Sir Albert Sakzewski Virus Research Centre Royal Children's Hospital Brisbane QLD4029 Australia

目的　观察记忆性CTL的抑瘤作用是否需要抗原特异性Th 细胞的辅助。方法　表达ovaT细胞表位SIINFEKL特异性TCR的T细胞转输Rag- - 小鼠,经相应T细胞表位多肽刺激后产生记忆性CTL ,将此记忆性CTL转输已产生特异性和非特异性Th 细胞的C5 7... 详细信息

目的　观察记忆性CTL的抑瘤作用是否需要抗原特异性Th 细胞的辅助。方法　表达ovaT细胞表位SIINFEKL特异性TCR的T细胞转输Rag- - 小鼠,经相应T细胞表位多肽刺激后产生记忆性CTL ,将此记忆性CTL转输已产生特异性和非特异性Th 细胞的C5 7bL 6小鼠体内并接种肿瘤细胞Eg7。结果　经T细胞表位多肽免疫后,SIINFEKL特异性TCRT细胞成功在Rag- - 小鼠体内增殖并分化为记忆性CTL ;抗原特异性Th 细胞可辅助产生较多效应性CTL但并没有完全的肿瘤抑制作用;记忆性CTL的完全抑瘤活性需要抗原特异性Th 细胞的辅助。结论　机体对肿瘤的长期完全杀伤作用不但需要肿瘤特异性抗原诱导产生的记忆性CTL ,而且需要特异性Th 细胞的辅助,肿瘤疫苗的设计必须包括特异性的CTL表位多肽和辅助性Th 细胞多肽。

关键词： Th细胞 CTL 记忆性作用研究 C57bL/6小鼠抗原特异性介导表位多肽肿瘤抑制作用 T细胞表位肿瘤特异性抑瘤作用肿瘤细胞非特异性体内增殖多效应性抗原诱导杀伤作用肿瘤疫苗 TCR 免疫后性需要辅助性

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多种细胞因子在哮喘大鼠发病中的作用

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中国组织工程研究与临床康复 2007年第27期11卷 5324-5327页

作者：陈莹戴晋锦州市中心医院儿科辽宁省锦州市121001 锦州市中心医院麻醉科辽宁省锦州市121001

目的:在建立大鼠哮喘模型基础上观察细胞因子的水平变化,探讨其可能的作用机制。方法:实验于2006-09/10在锦州医学院医学实验中心完成。①实验材料:清洁级8～12周龄SD大鼠45只,雌雄各半(22和23只),体质量(200±50)g。卵白蛋白(邦定泰克... 详细信息

目的:在建立大鼠哮喘模型基础上观察细胞因子的水平变化,探讨其可能的作用机制。方法:实验于2006-09/10在锦州医学院医学实验中心完成。①实验材料:清洁级8～12周龄SD大鼠45只,雌雄各半(22和23只),体质量(200±50)g。卵白蛋白(邦定泰克生物技术有限公司);百日咳杆菌菌苗(卫生部生物制品研究所菌苗室)。②实验分组:按随机法分为3组,每组15只,雌雄各半(7或8只),为正常对照组、哮喘模型组、地塞米松组。③实验干预:模型组、地塞米松组采用卵白蛋白注射雾化吸入致敏激发法复制哮喘模型。地塞米松组同时吸入地塞米松(剂量为1mg/kg)。正常对照组用等量生理盐水替代进行腹腔注射和雾化吸入。各组在最后1次雾化后,腹主动脉取血,取上清液备用。行支气管肺泡灌洗,回收支气管肺泡灌洗液,吸取上清液备用。④实验评估:均采用酶联免疫分析法测定血清及支气管肺泡灌洗液上清液中白细胞介素4,5,10,12,13,干扰素γ水平变化。结果:45只大鼠都存活,均进入结果分析。各组大鼠血清细胞因子水平及肺泡灌洗液细胞因子水平呈现相同的统计学结果,哮喘模型组白细胞介素4,5,13明显高于正常对照组(Ph亚群功能失衡理论不能完全解释哮喘的发生。

关键词：哮喘细胞因子类白细胞介素10 T淋巴细胞

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Function of helper T Cells in the Memory CTL-mediated Anti-tumor Immunity

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journal of Microbiology and Immunology 2004年第1期2卷 50-55页

作者：高丰光 germain j.P.Fernendo 刘文军 Department of Microbiology and Immunology Medical College Xiamen University Centre for Immunology and Cancer Research University of Queensland Princess Alexandra Hospital

To investigate the role of CD4 + helper T (Th) cells in the memory CTL-mediated anti-tumor immunity, the Rag-1 gene knock out mice were adoptively transferred with oT-1 cells to generate the memory CTL, the C57bL/6 mice immunized with the epitope peptide of ova specific Th cells and with different adjuvants were adoptively transferred with these memory-CTLs, and then the animals were challenged with tumor cells Eg7. It was found that although the simple immunization of mice with the epitope peptide of the ova specific Th cells could generate more effect CTL, but this effect was not so strong enough to resist completely the challenges with tumor cells. Nevertheless, the memory CTL-mediated anti-tumor immune effect required the helps of Th1 and Th2 cells. The cross-regulation between Th1 and Th2 cells seemed to be beneficial for the host to generate more effector CTL for mounting an efficient anti-tumor response. It concluded that the interaction between Th1 and Th2 cells might be more important than the single subset of Th cells in the memory CTL-mediated anti-tumor immune response. More attention should be paid in this regard for the future studies.

关键词： Memory T cells helper T cells Transgenic CD44

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Using Anti-Müllerian hormone (AMh) as a Predictor of ova Production for bovine Embryo Transfer

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Advances in Reproductive Sciences 2020年第1期8卷 36-47页

作者： j. T. jaques R. C. Cardoso j. Chachere S. Sinha R. Seery A. A. wilkes D. Forrest C. R. Looney

The objective of this study was to determine the relationship of anti-Müllerian hormone (AMh) to ova production in various breeds of cattle in an embryo transfer program. Various factors that were evaluated included breed type, age, weight, body condition and flush history as to their influence on total ova recovery. The superovulation regimen called for CIDR (Controlled Internal Drug Release) insertion and a 2 cc injection of Combo (25 mg progesterone and 1.25 mg of estradiol per mL (2 cc IM injection)) on day 0. Day 4, FSh treatments were initiated in both AM and PM with decreasing amounts over the next four days. Day 6, along with FSh, prostaglandin was given in the AM and PM. on Day 7, a final FSh injection and CIDR removal were done in the AM. This resulted in estrus and AI on day 8 and collection of ova on day 15. Results were drawn from analyzing 369 animals;Angus n = 25, black brangus n = 43, Red brangus n = 53, brahman n = 103, beefmaster n = 112, and wagyu n = 33. age of donors ranged from 1.6 years to 15.4 years at collection with an average age of 7.16 years of age. Analysis of results demonstrated that age clearly had a significant (P 0.05) on ova production. More importantly, we observed the total ova production was significantly (P ociated with the AMh concentration (the greater the AMh concentration, the greater number of ova per flush).

关键词： AMh ova Superovulation FSh Prostaglandin

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α<sub>2</sub>-macroglobulin co-administered <i>in vivo</i>promotes antigen delivery and presentation

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open journal of Immunology 2012年第2期2卷 72-77页

作者： Edith V. bowers jennifer E. bond george j. Cianciolo Salvatore V. Pizzo Department of Pathology Duke University Medical Center Durham USA

Administered in vivo, covalent receptor-recognized α2-macroglobulin (α2M*)-antigen complexes enhance humoral and cell-mediated immunity. we hypothesized that in vivo α2M*-encapsulation could be promoted in the setting of vaccines that co-deliver α2M* with unbound antigen, thereby eliminating the need to prepare complexes in vitro. Mice immunized intradermally with co-delivered α2M* and ova demonstrated antigen-specific immune responses, including anti-tumor responses, similar to those elicited by conjugated α2M*-ova complexes. Enhanced immunity appears to result from in vivo α2M*-encapsulation of antigen. This finding represents a significant advancement in the development of α2M* as an antigen delivery vehicle capable of enhancing the presentation of subunit vaccines.

关键词： α2-Macroglobulin-Antigen Complexes Antigen Presentation/Processing Vaccination Cytokines Spleen

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Surface geophysical Methods used to Verify the Karst geological Structure in the built-up Area:A Case Study of Specific Engineering-geological Conditions

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Acta geologica Sinica(English Edition) 2021年第5期95卷 1763-1770页

作者： Rene PUTISKA Marian MARSChALKo Isik YILMAZ Dominik NIEMIEC ChENg Xianfeng Ivan DoSTAL jan KUbAC Comenius University Faculty of Natural SciencesDepartment of Applied and Environmental GeophysicsIlkovičova 6BratislavaSlovakia VSb-Technical University of ostrava Faculty of Mining and GeologyInstitute of Geological Engineering17 listopadu1570833OstravaCzech Republic Cumhuriyet University Faculty of EngineeringDepartment of Geological Engineering58140 SivasTurkey Yunnan Land and Resources Vocational College Kunming 652501China

This article presents a research study of complex limestone karst engineering-geological conditions in the municipality Valaskanear banska bystrica in *** aim of the study is to demonstrate the impossibility of spatial identification of cave spaces using surface geophysical methods due to the specific engineering-geological conditions of a thick surface layer of anthropogenic fill containing highly heterogeneous anthropogenic *** maximum thickness is 3 *** specificific condition of the study area is its location in the built-up area,due to which the applicability of geophysical methods was *** article contains methodological recommendations to be used in analogous geological conditions with karst structures topped with anthropogenic fill,which complicates the identification of cave *** recommended solution herein is the identification of the cave system using underground mapping of the karst and its projection onto the surface for which surface geophysical methods have been combined.

关键词： karst engineering geology limestone dolomite anthropogenic fill complicated engineering-geological conditions geophysical study

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