地塞米松对哮喘大鼠Th1/Th2失衡及嗜酸性粒细胞凋亡的作用

目的　观察地塞米松对哮喘大鼠Th1/Th2 (T辅助细胞 1/T辅助细胞 2 )平衡、嗜酸性粒细胞 (EOS)凋亡率的影响作用 ,探讨糖皮质激素治疗哮喘的机制。方法　清洁级雄性SD大鼠 30只 ,随机分为 3组 :正常对照组 (C)、哮喘组 (A)、地塞米松治疗组 (T)。卵清白蛋白复制大鼠哮喘模型 ,检测大鼠血、支气管肺泡灌洗液 (BALF)中IL 4、IFN γ水平及气道壁EOS凋亡率。结果　A组大鼠BALF中IFN γ水平明显低于C组 (P <0 0 1) ,血中及BALF中的IL 4水平则明显高于C组 (均为P<0 0 1) ,表现出明显的Th1/Th2失衡。T组大鼠IL 4的表达明显低于A组而IFN γ的表达则明显高于A组 (均为P <0 0 1)。在A组 ,大鼠气道壁EOS的浸润明显增多 ,但凋亡细胞却很少看到 ,EOS凋亡率明显低于C组 (P <0 0 1) ,T组EOS凋亡率则明显高于A组 (P <0 0 1)。结论　纠正哮喘Th1/Th2失衡和促进气道壁EOS凋亡可能是糖皮质激素减轻哮喘气道炎症的重要机制之一。     

激活诱导细胞死亡对尖锐湿疣患者TH1/TH2细胞分化的影响

按1991年国家制订尖锐湿疣(CA)诊断标准确诊的31例患者为观测对象,其中男2 5例,女6例,年龄为19～4 8岁,平均年龄35岁,病程1个月以上36个月以下。所有患者均为近2个月内未接受免疫调节剂治疗,不伴有自身免疫性疾病、系统性疾病及其它感染性疾病。31例正常对照者为来自本院健康体检的正常人群,其中男2 3人,女8人。年龄为2 0～4 6岁,平均年龄31岁。近1个月内无感染史。观测对象以无菌手术抽取肝素抗凝全血5～10ml,在无菌条件下,经Ficoll密度梯度离心分离PBMC洗涤后,用RPMI 16 4 0 (附加10 %灭活小牛血清、青霉素10 0U ml及链霉素10 0 μg …     

嗜酸性粒细胞凋亡与支气管哮喘的关系

细胞凋亡是细胞在自身基因调控下进行的一种主动死亡,具有独特的形态结构和生物化学特征。嗜酸性粒细胞凋亡参与了支气管哮喘的发生和发展,糖皮质激素等药物可通过多种途径诱导嗜酸性粒细胞凋亡,使气道内嗜酸性粒细胞减少,减轻气道炎症,缓解病情     

口服卡介苗对哮喘小鼠TH1/TH2平衡的影响

卡介苗不仅被应用于结核病的预防,还应用于哮喘、慢支、肿瘤等疾病的治疗,国内外学者以皮内注射卡介苗用于实验性哮喘的治疗取得了很好的疗效。但卡介苗口服用于哮喘防治国内还未见报道。本实验通过口服卡介苗后哮喘小鼠支气管肺泡灌洗液(BALF)和外周血中IL-4、IFN-γ水平的变化,并用流式细胞仪来检测Y_H1/T_H2细胞平衡的影响,进一步探讨哮喘发病机理,为口服卡介苗治疗哮喘提供理论依据。32只BALB/c小鼠分为正常对照组、哮喘组、皮内注射卡介苗 哮喘组、口服卡介苗 哮喘组,以卵蛋白(OVA)致敏激发建     

鼻息肉组织TH细胞亚群与嗜酸性粒细胞浸润

鼻息肉的发生机制尚不确定,细菌、真菌感染,变态反应可能作为触发因素。鼻息肉组织含大量嗜酸性粒细胞和淋巴细胞,可能在鼻息肉发生中起重要作用。功能不同的T_H细胞存在的证据对基础和临床免疫学产生了重大影响。本研究通过流式细胞术测定不同类型鼻息肉组织T_H1及T_H2细胞百分率,HE切片嗜酸性粒细胞计数,以评价感染因素和变态反应因素在鼻息肉发生中的作用,明确T_H细胞与嗜酸性粒细胞增多的关系,指导鼻息肉分型和治疗。     

川崎病TH1/TH2功能状态的研究

川崎病(Kawasaki disease,KD)是一种急性弥漫性血管炎,婴幼儿发病多见,至今,该病病因及发病机理不明,从病人的流行病学特征推测可能与病原体感染或毒素超抗原引起免疫学异常有关.本研究通过对KD患儿急性期、恢复期PPD皮试的观察以及外周血血清IgE的变化、外周血CD4 T细胞CD30表达和外周血单个核细胞(PBMC)培养上清IL-4、IFN-γ水平的测定,了解KD急性期TH1/TH2功能平衡状态及免疫发病机理.     

HIV感染中TH1／TH2转换的争议

本文综述了近年来有关ＨＩＶ感染期间ＴＨ１→ＴＨ２转换的学说及其争议。进一步探讨ＨＩＶ感染的发病机理。     

卡介苗对哮喘小鼠TH1/TH2平衡的影响

目的　探讨卡介苗 (BCG)对哮喘小鼠TH1 TH2平衡的影响。方法　C5 7BL 6小鼠以卵白蛋白 (OVA)致敏激发建立哮喘模型。于第一次抗原激发前 2周以BCG皮内注射干预 ,在最后 1次抗原激发后 4 8h收集支气管肺泡灌洗液 (BALF)和外周血 ,ELISA方法测定外周血清及BALF中IL 5与IFN γ水平 ,并采用三色光流式细胞分析法测定外周血TH1 TH2细胞比。结果　与阴性对照组相比 ,OVA致敏激发组外周血清及BALF中IL 5水平升高而IFN γ水平降低 ,BCG干预组外周血清及BALF中IL 5较OVA致敏激发组低而IFN γ较后者升高 ,与阴性对照组水平相近。此外 ,OVA致敏激发组外周血中TH2 TH1比值 (1.5 7± 0 .5 6 )较阴性对照组 (0 .37± 0 .0 5 )明显增高 (P <0 .0 1) ,BCG干预后TH2 TH1比值 (0 .5 9± 0 .11)较OVA致敏激发组下降 (P <0 .0 5 ) ,同时Tc2 Tc1比值 (0 .6 2± 0 .0 7)也较OVA致敏激发组 (1.15± 0 .18)降低 (P <0 .0 5 )。结论　哮喘小鼠中TH2型免疫应答占优势 ,BCG干预不仅在细胞因子水平 ,也在细胞数量上校正了TH1 TH2失平衡。     

卡介菌多糖核酸和地塞米松对口腔扁平苔藓TH1/TH2细胞因子的调节作用

口腔扁平苔藓 (orallichenplanus ,OLP)是T淋巴细胞介导的免疫反应 ,其主要病理变化为固有层大量的T淋巴细胞呈带状浸润〔1〕 。卡介菌多糖核酸(BacillusCalmette Guerinpolysaccharidenucleicacid ,BCGPSN)是从卡介菌中经热酚法提取的一种具有免疫调节功能的免疫调节剂 ,对慢性支气管炎、哮喘等疾病有较好的疗效。本研究拟通过观察BCGPSN和地塞米松对OLP患者外周血单个核细胞 (peripheralbloodmononuclearcells ,PBMC)IFN γ和IL 4的调节作用 ,探讨OLP患者的TH1 TH2免疫应答模式及BCGPSN和糖皮质激素对OLP患者TH1 TH2…     

慢性乙型肝炎病人HBcAg特异性CTL的体外诱导及活性

目的 从慢性乙型肝炎病人外周血单个核细胞（PBMC）中诱导和扩增乙型肝炎病毒核心抗原（HBcAg）特异性细胞毒性T淋巴细胞（CTL）。方法 含乙型肝炎病毒重组逆转录病毒载体转染病人自身永生化B细胞作为抗原递呈细胞,联合重组HBcAg和IL-2,从病人PBMC中诱导和扩增HBcAg特异性CTL,^51Cr释放法检测其细胞毒活性。结果 此方法诱导的TCL可以有针对性的杀伤靶细胞,而不能够杀伤空载体转染及未经转染的B细胞。结论 所建立的方法可以在慢性乙型肝炎病人的PBMC中诱导出HBcAg特异性CTL活性。     

TH1型/TH2型细胞因子对滋养层及蜕膜内分泌功能的影响

目的　探讨辅助T细胞 (TH) 1型 / 2型细胞因子对人绒毛组织及蜕膜组织内分泌功能的影响。方法　应用新鲜绒毛组织和蜕膜组织建立体外分泌人绒毛膜促性腺激素 (hCG)及催乳素(PRL)的模型。hCG及PRL的分泌水平应用放免法 (RIA)进行分析测定。结果　TH1型细胞因子γ干扰素 (IFN γ)在一定的浓度范围内 (10～ 10 0 0ng/ml)对绒毛组织分泌hCG有明显的抑制作用 (P <0 .0 1) ;而TH2型细胞因子白细胞介素 4 (IL 4 ) (1～ 10ng/ml)则有明显的促进作用 (P <0 .0 1)。TH1型细胞因子IFN γ低浓度时 (1～ 10ng/ml)对蜕膜组织分泌PRL有刺激作用 (P <0 .0 5 ) ,高浓度时 (10 0～10 0 0ng/ml)则有抑制作用 (P <0 .0 1) ;TH2型细胞因子IL 4对PRL分泌的调节作用与对hCG分泌的作用相类似。结论　TH1型 /TH2型细胞因子可能通过影响滋养层及蜕膜内分泌功能而在早期妊娠中起重要的免疫调节作用。     

Immunologic influences on allergy and the TH1/TH2 balance

TH2 cell-mediated immune responses against "innocuous" antigens play a triggering role in atopic allergy. Several epidemiologic studies have clearly shown that the reduced microbial exposure of children caused by the westernized lifestyle is responsible for the increased prevalence of allergy that has occurred in the last decades in developed countries ("hygiene hypothesis"). The immunologic changes caused by the reduced exposure to pathogenic and nonpathogenic microbes during childhood are still controversial. The initial interpretation has been a lack of shift of allergen-specific responses from the TH2 to the TH1 phenotype. This is because of reduced production of IL-12 and IFNs by cells of the natural immunity stimulated by bacterial products through their Toll-like receptors (missing immune deviation). Another interpretation emphasizes the importance of reduced activity of T-regulatory cells (reduced immune suppression). However, although there are impressive amounts of data in favor of the missing immune deviation, experimental evidence supporting the role of reduced immune suppression in explaining the increased prevalence of allergy is currently weak or even contradictory. The solution to this question is very important not only from a theoretic point of view but also because of its therapeutic implications.     

肾综合征出血热患者TH1/TH2、Tc1/Tc2亚群比例及有关细胞因子变化的研究

目的：探讨肾综合征血热（HFRS）患者TH1样和TH2样细胞平衡状态以及血清中细胞因子的变化，方法：收集HFRS患者和健康个体血清，采用夹心ELISA方法测定IFN－γ、IL－4和TNF－α的水平，分离PBMC，采用三色流式细胞术分析HFRS患者CD4^ T细胞和CD8^ T细胞中IFN－γ^ 和IL－4^ 细胞的百分率。观察HFRS患者TH1／TH2，Tc1/Tc2比例的变化，比较了不同病程和病情HFRS患者血清中上述指标的变化，结果：HFRS患者血清中TH1类和TH2类细胞因子水平均明显升高，其中IFN－γ和IL－4的平均水平显著高于健康个体（P＝0．016，P＝0．019）。HFRS患者PBMC中TH1、TH2、Tc1,Tc2细胞的平均百分率均高健康个体Tc细胞比例的改变较TH细胞明显，TH1样细胞的比例较TH2样细胞变化明显。发热期患者血清中IFN－γ、IL－4和TNF-α的水平明显升高于恢复期患者，发热期的重症患者的IFN－γ水平升高较轻症明显。结论：HFRS患者血清中IFN－γ和IL－4水平以及PMBMC中TH1、TH2、Tc1和Tc2细胞的比例均有所升高，发热期的患者和重症HFRS患者上述参数变化更明显，表明感染机体总体的免疫平衡偏向TH1类。     

In vitro studies of the interaction between heparin and eosinophil cationic protein

Eosinophil cationic protein (ECP) is a protein specific to the granules of human eosinophil granulocytes, ECP is highly cationic and may damage tissue if not inactivated. Heparin is a highly anionic substance present in mast cells and basophil granulocytes. The present in vitro study shows that ECP can inactivate the anticoagulant activity of heparin probably by the formation of a complex between the two molecules. This function may be of importance for the microenvironment of allergic diseases where secretion of heparin may promote penetration of mast cell products through tissues. Also this may constitute one mechanism whereby the cytotoxic action of ECP is neutralized.     

Recombinant Interleukin-2 Corrects In Vitro the Immunological Defect of Endometriosis

PROBLEM: It has been shown recently that women with endometriosis have several immunological defects. In particular, these patients have a defect in peripheral blood natural killer cell activity and have lost their capacity of recognizing and lysing autologous endometrial cells. METHOD: We evaluated the effect of recombinant interleukin-2 (rIL-2) on peripheral blood lymphocytes obtained from both healthy donors and endometriosis patients. The generation of a strong cytolytic activity against autologous endometrial cells was obtained from both normal donors and endometriosis patients. RESULTS: Interestingly, these cytolytic cells belong to the T-cell lineage and do not recognize both autologous keratinocytes and allogeneic endometrial cells, thus suggesting a mechanism of specific recognition of autologous cells. CONCLUSION: The capability of restoring cytolytic activity using rIL-2 suggests a new immunotherapeutic approach for the treatment of severe endometriosis.     

Antibodies to acetylcholine receptors in myasthenia gravis. In vitro synthesis by peripheral blood lymphocytes before and after thymectomy.

Pokeweed mitogen (PWM)-driven in vitro synthesis of antibodies to the acetylcholine receptor (PSA) was studied in non-thymoma patients with myasthenia gravis. In a group of 46 patients, the occurrence of PSA was related to the presence of the thymus or, in operated patients, the absence of a clinical effect of thymectomy. Sixteen patients were followed before and soon after thymectomy. PSA disappeared in all patients, at least temporarily, between 6 weeks and 1 year afterwards, independent of the clinical course and eventual clinical effect of the operation. A recurrence was found only in one of the five patients who derived no benefit from the operation. These findings support the hypothesis that the therapeutic effect of thymectomy can be explained by removal of a source of autoreactive lymphocytes. There was no correlation between the changes in serum levels of a-AChR and clinical improvement, suggesting a minor role of circulating peripheral blood lymphocytes (PBL) and the thymus in the total production of a-AChR.     

BCG30主要分泌蛋白对尘螨变应性患者TH1/TH2平衡调节作用的观察

目的　研究结核杆菌相对分子质量 (Mr)为 30× 10 3的主要分泌蛋白 (BCG30 ,也称Ag85B)对尘螨变应原过敏所致的哮喘等变应性患者外周血单个核细胞 (PBMC)分泌TH1、TH2细胞因子的调控作用。方法　常规分离 2 7例尘螨过敏的变应性患者 (A) ,其中 18例哮喘患者 (A1)、9例变应性鼻炎或皮炎患者 (A2 )和 13例正常人 (B)的PBMC ,在离体与螨变应原、BCG30单独或复合共培养 ,ELISA法测定培养上清IL 5、IFN γ的水平。结果　A、A1、A2、B 4组无刺激状态下的IL 5、IFN γ水平无差异 (P >0 .0 5 )。尘螨变应原刺激可显著促进A、A1、A2 3组PBMC分泌IL 5 ,P均 <0 .0 5 ,同时 ,A组的IFN γ水平自身比较亦明显增高 (73.5 8pg ml± 30 .2 3pg mlvs 30 .71pg ml± 18.87pg ml,P <0 .0 5 )。将尘螨变应原与BCG30和PBMC进行复合培养 ,并与单独尘螨变应原刺激组比较 ,其IFN γ水平在A组 (92 .89pg ml± 2 9.0 7pg mlvs 73.5 8pg ml± 30 .2 3pg ml)和A1组 (87.6 0pg ml± 36 .4 5pg mlvs 5 8.75pg ml± 7.84pg ml)均较后者为高 (P均 <0 .0 5 ) ,且A组的IFN γ IL 5的比值较单独尘螨变应原刺激组显著增高 (5 .0 3± 1.36vs 4 .2 0± 1.6 4 ,P <0 .0 5 ) ,而A1组其比值亦有增高趋势 (P =0 .0 7)。正常人中各刺激组间所有指标均     

Comparison of the T lymphocyte-dependent induction of angiotensin-converting enzyme and leucine aminopeptidase in cultured human monocytes.

The T lymphocyte-mediated induction of angiotensin-converting enzyme (ACE) in cultured autologous peripheral blood monocytes has been proposed as a model system for the investigation of the in vivo induction of ACE in the monocyte-derived granuloma epithelioid cells of some granulomatous diseases such as sarcoidosis. The studies described here were designed to evaluate the specificity of the model system by comparing the parameters for induction of ACE with those for the induction of another monocyte metallo-ecto-peptidase, leucine aminopeptidase (LAP). The concentration of LAP in freshly isolated monocytes was 0.09 mU/10(6) monocytes (s.e.m. 0.04) and increased to a maximal value of 0.19 mU/10(6) monocytes (s.e.m. 0.32) after 3 days when monocytes were cultured alone. ACE was not detectable in freshly isolated monocytes. However, after 6 days of culture, monocytes contained 0.22 mU ACE/10(6) monocytes (s.e.m. 0.04). Comparison of the levels of ACE and LAP induced during culture of monocytes alone indicated that the induction of these two enzymes were correlated. The induction of both enzymes was further enhanced by the presence of T lymphocytes in a dose-dependent manner. At 4 x 10(6) T lymphocytes per culture, ACE levels increased to 1.81 mU/10(6) monocytes (s.e.m. 0.24) and LAP levels to 1.03 mU/10(6) monocytes (s.e.m. 0.35). The enhancement of ACE activity required autologous lymphocytes, while heterologous T lymphocytes were equally effective in inducing LAP. Comparison of the levels of ACE and LAP induced during coculture of autologous T lymphocytes and monocytes from 21 independent donors, demonstrated no correlation between the induction of ACE and LAP. These data indicate that, although T lymphocytes also enhance the induction of LAP, the underlying mechanism must differ from that of ACE induction.     

Distinct effects of anti-tumor necrosis factor combined therapy on TH1/TH2 balance in rheumatoid arthritis patients

The immune balance in patients with rheumatoid arthritis (RA), a disease characterized by TH1 dominance, treated by the preferred combined anti-tumor necrosis factor (anti-TNF) and methotrexate (MTX) therapy was evaluated by assessing the chemokine and cytokine receptors as well as apoptosis induction. A meta-analysis of combined therapy by TNF blockers and MTX in 15 RA patients, MTX monotherapy in 20 RA patients, and 11 diagnosed but untreated RA patients was performed by assessing several immune markers in the whole lymphocyte population, as well as in specific CD4 cells, by both flow cytometry and image analysis. A significant downregulation of CXCR3 and IL-12 receptors (both TH1 markers) and a significant increase in the chemokine receptor CCR4 and, to a lesser extent, IL-4R (both TH2 markers) were found; a particularly marked increase was found in patients treated by combined therapy. This phenomenon was pronounced in CD4 cells and was accompanied by a high proportion of apoptotic cells. The therapeutic effect of MTX and TNF blockers may be due to apoptosis induction in lymphocytes infiltrating from the inflammation site and restoring the TH1/TH2 balance.