外周血T细胞亚群及细胞因子对外源性哮喘IgE生成…

对３０例哮喘患者及３０例健康成年人的外周血，采用单克隆抗体（ＭｃＡｂ）间接免疫荧光法测定Ｔ细胞亚群；ＥＬＩＳＡ双抗体夹心法测定ＩｇＥ、ＩＬ－４；ＦＩ２细胞株，生物学方法测定ＩＬ－２；ＩＬ－６依赖细胞株７ＴＤ１，掺入法测定ＩＬ－６；用抗人ＣＤ２３的ＭｃＡｂ测定ＣＤ２３。为研究Ｔ细胞、细胞因子对哮喘ＩｇＥ生成调节机理及细胞因子在哮喘发病过程中的作用。结果显示：发作期ＩｇＥ、ＩＬ－２、ＩＬ－４、ＣＤ２３     

人类TH细胞亚群与支气管哮喘

本文列举了人类存在Ｔ辅助细胞（ＴＨ）功能性亚群（ＴＨ１和ＴＨ２）的证据；叙述调节ＴＨ细胞亚群分化的因素，尤其是ＴＨ１和ＴＨ２相互制药作用；并讨论了ＴＨ２细胞在支气管哮喘慢性气管炎症形成中作用，为防治哮喘提供新的思路。     

分泌细胞因子的CD8^＋T细胞亚群研究进展

Ｔ细胞具有功能不同的亚群，其中ＣＤ４＾＋辅助Ｔ细胞（ＴＨ）的亚群分类及功能早已成定论。近几年的研究发现传统的ＣＤ８＾＋细胞毒Ｔ细胞（ＣＴＬ）也可分泌与ＣＤ４＾＋Ｔ细胞相似的细胞因子，也可分为两类亚群，分别定义为Ｔｃ１和Ｔｃ２。本文就近年来这方面的研究进展作一综述。     

发作期哮喘患者外周血T细胞亚群、B细胞和NK细胞的变化及临床意义

目的：探讨发作期哮喘患者外周血T细胞亚群、B细胞和NK细胞变化及临床意义。方法：采用直接免疫荧光法,用流式细胞术检测30例发作期哮喘患者和30例正常人对照的T细胞亚群、B细胞和NK细胞的变化。结果：与正常对照组比较,发作期哮喘患者CD4^＋T细胞、CD19^＋B细胞和CD4^＋／CD8^＋比值显著增高（P〈0．01）,CD8^＋T细胞显著下降（P〈0．01）和CD56^＋CD16^＋NK细胞下降（P〈0．05）。CD3^＋T细胞无明显变化。结论：发作期哮喘患者的免疫功能紊乱在哮喘发病中起着重要作用。     

人外周血中γδT细胞亚群、表型和细胞因子产生的研究

目的进一步比较人外周血中γδT细胞及Vδ1^+、Vδ2^+、Vδ1^-Vδ2^-细胞频率、表型及功能方面异同,进一步了解γδT细胞在免疫应答中的作用。方法分离人外周血单个核细胞(PBMCs),流式细胞术检测TCRγδ、Vδ1、Vδ2、CD4、CD8、CD45RO、CD62L、Granzyme A。PMA+Ionomycin刺激前后检测细胞因子IFN-γ、IL-17A及转录因子T-bet、Ro Rγt水平。磁珠富集、流式分选和ELISA检测纯化细胞IFN-γ产生。结果根据γδT细胞受体(TCRγδ)δ链,将γδT细胞分为Vδ1^+,Vδ2^+,Vδ1^-Vδ2^-3群,TCRγδ高低表达与Vδ1、Vδ2表达相关。Vδ1^+、Vδ2^+细胞约有20%~40%细胞表达CD8,低表达CD4,而Vδ1^-Vδ2^-细胞约有60%表达CD8和20%表达CD4。约6%的Vδ1^+和30%的Vδ1^-Vδ2^-细胞表达CD45RO,而约有80%的Vδ2^+细胞表达CD45RO。刺激后,γδT细胞3个亚群均表达IFN-γ和IL-17,Vδ2^+细胞表达最高,3个亚群差异有显著性,与纯化细胞结果相符。3个亚群细胞均高表达转录因子T-bet和Ro Rγt,高表达颗粒酶A。结论人外周血中Vδ1^+、Vδ2^+及Vδ1^-Vδ2^-细胞在频率、表型及功能方面均有显著差异,均可产生高水平细胞因子IFN-γ,该结果将为γδT细胞进一步研究打下良好基础。     

支气管哮喘患儿外周血B细胞和T细胞及其亚群的研究

目的 :探讨了支气管哮喘患儿外周血B细胞和T淋巴细胞及其亚群的变化。方法 :应用单克隆技术测定了 38例支气管哮喘患儿外周血B细胞和T淋巴细胞亚群的水平并以 30名正常健康人作比较。结果 :支气管哮喘患儿外周血B细胞数显著地高于正常人组 (P <0 .0 1 )CD3 、CD4、CD4/CD8显著地低于正常人 (P <0 .0 1 )。结论 :支气管哮喘是一种自身免疫调节异常的疾病     

T细胞亚群及其细胞因子在原发性肾小球病中的变化

为观察不同病理类型原发性肾小球病患者的外周血中CD3、CD4和CD8三种T细胞亚群 ,及Th1和Th2所分泌的代表性细胞因子IL 4、IL 10和TNF α的变化 ,从而分别取原发性肾小球病患者的全血和血清 ,采用流式细胞技术测定T细胞亚群 ,ELISA法测定细胞因子IL 4、IL 10和TNF α。结果是原发性肾小球病组中CD3+ 、CD8+ 细胞比例增高 ,而不同类型的肾炎 ,T细胞亚群的变化不尽相同。微小病变型、系膜增生型和膜性肾病患者表现为IL 4增高 ,而IgA肾病患者则降低 ;四种不同的病理类型病人的IL 10均降低 ,尤以IgA肾病最明显。膜性肾病、微小病变型、系膜增生型肾炎患者Th2细胞功能增强 ;IgA肾病患者有Th1优势应答的可能 ;IL 10的水平明显降低可能是原发性肾小球病发生发展的重要机制之一     

Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma

BACKGROUND: Type 1 dendritic cells (DC1) express the high-affinity IgE receptor (FcepsilonRI); however, the regulation of FcepsilonRI expression by DCs is not well understood. Type 2 DC (DC2) expression of FcepsilonRI has not been demonstrated. OBJECTIVE: We hypothesized that DC2 cellsalso express FcepsilonRI and that expression of FcepsilonRI by the DC1 and DC2 subsets correlates with serum IgE and allergic asthma disease status. METHODS: To test these hypotheses, we quantitated FcepsilonRI alpha chain expression by the peripheral blood precursor DC1 (pDC1) and pDC2 subsets by using flow cytometry. RESULTS: FcepsilonRI was expressed by the pDC1 and pDC2 subsets, as well as tissue DCs from tonsils. Relative FcepsilonRI expression by basophil, pDC1, and pDC2 subsets was 12:6.5:1, respectively. In both pDC subsets, FcepsilonRI expression was significantly greater in allergic asthmatic subjects than in nonatopic control subjects. pDC1 and pDC2 expression of FcepsilonRI was highly correlated to serum IgE concentration. The pDC1, pDC2, and basophil subsets demonstrated a similar magnitude of increase in FcepsilonRI expression relative to changes in serum IgE. CONCLUSIONS: FcepsilonRI expression is characteristic of both the DC1 and DC2 subsets. Furthermore, FcepsilonRI expression by these cells is highly correlated to serum IgE and to basophil FcepsilonRI expression and is greater in subjects with allergic asthma. These data support the concept that novel therapeutic approaches directly targeted at FcepsilonRI expression would affect both the sensitization and the effector phases of the allergen-specific immune response.     

卡介苗对哮喘小鼠气道炎症、TH细胞分化及血清OVA特异性IgE的影响

目的 探讨卡介苗（BCG）对哮喘小鼠气道炎症、TH细胞分化及血清OVA特异性IgE的影响。方法 动物随机分为阴性对照组、OVA致敏激发组和BCG干预组。检测气管血管旁嗜酸性粒细胞（EOS）数目、气管上皮杯状细胞增生指数和黏液储存指数、小鼠外周血上清液中细胞因子白细胞介素5（IL-5）及γ干扰素（IFN-γ）浓度、小鼠肺组织中T-bet和GATA-3mRNA水平及小鼠血清中OVA特异性IgE表达。结果BCG干预组和OVA致敏激发组中小鼠肺气管血管旁单位面积EOS数目分别为（65．09±32．58）个/mm^2、（941．86±592．03）个/mm^2，两者比较差异有统计学意义（P〈0．05）；BCG干预组和OVA致敏激发组杯状细胞增生指数分别为（19．25±12．27）个／mm、（54．39±24．50）个／mm，BCG干预组和OVA致敏激发组黏液储存指数分别为（6．47±3．94）％、（15．53±11．38）％，两者比较差异有统计学意义（P〈0．001）；BCG干预组和OVA致敏激发组IL-5浓度分别为（83．40±11．33）pg／ml、（192．30±44．30）pg/ml，1FN-γ浓度分别为（28．69±6．05）pg/ml、（18．12±3．78）pg/ml，T-bet／GATA．3mR—NA比值分别为1．02±0．18、0．74±0．07，两者比较均差异有统计学意义（P〈0．01）；BCG干预组和OVA致敏激发组血清中OVA特异性IgE的表达分别为0．61±0．27、1．05±0．45，两者比较差异有统计学意义（P〈0．05）。结论 BCG能抑制哮喘小鼠气道EOS浸润和黏液高分泌状态，影响T-bet／GATA-3表达水平，降低IL-5水平而增高IFN-γ水平，并能抑制哮喘小鼠血清中OVA特异性IgE的表达。     

支气管哮喘的细胞因子治疗进展

哮喘是一种慢性气道炎症性疾病,它的发生和发展与多种细胞因子密切相关.目前哮喘还没有有效的预防和治愈方法,细胞因子抑制剂已经作为潜在的治疗手段而被广泛研究.其中IL-4、IL-5、TNF-α抑制剂的临床研究已经取得了突破性的进展.IL-13和IL-9的临床试验正在研究中.对哮喘动物模型的大量研究发现了胸腺基质淋巴细胞生成素(TSLP),IL-17等新的相关细胞因子,这为哮喘细胞因子治疗提供了新的思路.而多种细胞因子抑制剂的联合使用也为治愈哮喘提供了可能.同时,哮喘个体化医疗的研究为逆转哮喘提供了有力保障.     

Probiotics and diseases of altered IgE regulation: A short review

The use of probiotics has gained considerable popularity in the marketplace in the US and has been steadily increasing due to consumer interest in potential treatment of various diseases, which may be due to modulation of immune responses. The aim of this review is to present information from representative studies regarding some of the possible applications and clinical effects of probiotic use in diseases of altered immunoglobulin (IgE) regulation (allergic rhinitis (AR), asthma, atopic dermatitis (AD) and food sensitization). Reports in humans are sparse or controversial; there is currently little reliable scientific data that supports the theory that there exists a cause–effect relationship between taking probiotics and alleviation of allergic disease. Unfortunately, these findings are too variable to allow substantial conclusions as to the efficacy and effectiveness of probiotic use in these disease states.     

哮喘家系成员血清总IgE的遗传学分析

目的 探讨哮喘家系成员血清总IgE的遗传方式。方法 收集哮喘遗传家系，用酶联免疫吸附测定方法检测哮喘家系成员病人和正常人的血清总IgE，并取无哮喘家族史和无过敏家族史的正常人作为对照组，进行总IgE的遗传分析。结果 哮喘家系成员的血清总IgE分布是双形态分布，父母一方及其子女IgE超常的占56％，父母双方及其子女IgE超常的占50％。结论 总IgE可能是以单基因遗传控制为主，且总IgE的超常(H)可能是因常染色体显性遗传伴不完全外显。     

Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colonystimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopics asthmatics,and atopic and nonatopic controls

Specific eosinophil accumulation and activation within the asthmatic bronchial mucosa are thought to occur at least partly through the actions of cytokines, including interleukin (IL)-5, IL-3 and granulocyte/macrophage colonystimulating factor (GM-CSF). Although mRNA encoding some of these cytokines has been demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies from asthmatics, it has yet to be established whether these cells produce the translated products and whether expression is associated with CD4⁺ T helper or CD8⁺ cytotoxic T cells. We addressed this problem by raising polyclonal CD4⁺ and CD8⁺ T cell lines from the BAL fluid of six atopic asthmatics, five atopic non-asthmatics and seven non-atopic non-asthmatic controls. BAL fluid cells obtained at fiberoptic bronchoscopy were depleted of adherent cells, and then T lymphocytes expanded by stimulation with monoclonal anti-CD3 antibody and recombinant human IL-2. When lymphocytes had expanded to sufficient numbers, CD4⁺ and CD8⁺ cells were separated by positive selection with magnetic beads coated with anti-CD4 or anti-CD8 monoclonal antibodies and further expanded. Cytokine secretion by standardized cell numbers was measured by enzyme-linked immunosorbent assays. BAL CD4⁺ T cell lines from the asthmatics secreted significantly elevated quantities of both IL-5 and GM-CSF as compared with lines from the atopic and non-atopic controls (p = 0.023–0.003). In contrast, IL-3 secretion did not significantly differ between the groups. In some subjects, CD8⁺ T cell lines also secreted significant quantities of these cytokines and there was a trend for IL-5 secretion by these cells to be higher in asthmatics than non-atopic controls (p = 0.035). These data are consistent with the hypothesis that activated T lymphocytes from asthmatics, particularly of the CD4⁺ subset, are predisposed to release elevated quantities of cytokines relevant to the accumulation and activation of eosinophils.     

T and B cell immune response to a 55-kDa endothelial cell-derived antigen in severe asthma

Current concepts on the pathogenesis of chronic asthma emphasize the role of several inflammatory cell populations and their respective mediators that interact in a complex network. However, beside inflammatory cells, lymphocytes are also present in asthmatic airways. Although little is known about their involvement in asthma, it has been suggested that lymphocytes may participate in the development of chronic inflammation either through lymphokine secretion or through antibody production. In this study, we describe circulating IgG autoantibodies, directed against a common 55-kDa antigen shared by platelets and cultured endothelial cells, and found in 34 out of 97 asthmatic patients. Among epidemiological, clinical and biological characteristics of these asthmatic patients, the anti-55-kDa antigen antibodies are mainly restricted to patients with negative cutaneous prick tests (p = 0.0014), and corticosteroid-dependent asthma (p = 0.0036). These antibodies were also detected in a few patients with autoimmune disorders like systemic lupus erythematosus (3/30) or rheumatoid arthritis (2/36). Both platelet and endothelial cell antigens were cross-reactive, had an isoelectric point between 8.0 and 9.0, were unsensitive to reducing agents such as 2-mercaptoethanol. and were not present on either platelet or endothelial cell surface, as determined by immunostaining assay. [³H] Thymidine incorporation assay with peripheral blood mononuclear cells from patients in the presence or in the absence of 55-kDa antigen, purified from nitrocellulose sheets demonstrated a specific incorporation in 6 out of 13 patients with circulating anti-55-kDa antigen antibodies, with index values ranging from 12 to 3. Such a T cell reactivity has also been observed in 3 out to 17 patients without detectable serum anti-55-kDa antigen antibodies. Moreover, a significant correlation was found between index values of antigen-specific T cell reactivity and the forced expiratory volume in one second (r = 0.544, p = 0.003). Our data indicate that the detection of such antibodies allows to distinguish a subgroup of asthmatics in terms of severity and to suggest a relationship between clinical severity and T and B cell autoreactivity to the 55-kDa platelet/endothelial cell antigen.     

细胞因子介导的抗菌蛋白表达调控机制

抗菌蛋白是机体先天性防御系统的构成成分,在防御病原人侵方面起十分重要作用。虽然一些抗菌蛋白成分的表达是组成性的,但最新研究表明,许多抗菌蛋白的表达受到相关细胞因子的调控。尤其是T细胞系来源的细胞因子所发挥的作用最为显著。了解细胞因子介导的抗菌蛋白表达调控机制及IL-17和IL-22如何通过调节局部的相关抗菌蛋白表达来保持皮肤和粘膜免疫稳态性的很重要。     

IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma

Respiratory syncytial virus (RSV) causes lower respiratory tract disease in infants and young children, and is a public health concern, as is the increase in pediatric asthma. Respiratory viral infections may trigger asthma exacerbations. However, it remains unknown whether RSV infection may have a specific association with asthma. Total serum IgE, and IgE- and IgG-anti-RSV Ab responses were studied in older asthmatic compared with non-asthmatic children (M/F, mean age: 14) (N = 30, N = 43, respectively). We found: (1) total serum IgE was higher in asthmatic compared with non-asthmatics (P < 0.001); (2) total serum IgE did correlate with IgE anti-RSV Abs (P < 0.001), and with IgG anti-RSV Abs (P = 0.008) in all subjects; (3) total serum IgE levels did correlate with IgE anti-RSV in asthmatics (P = 0.047), but not in non-asthmatics (P = 0.13); (4) IgE anti-RSV Abs did correlate with IgG anti-RSV Abs in all subjects (P = 0.001); (5) IgE- and IgG-anti RSV Abs were higher in asthma compared with no asthma (P = 0.003; <0.001, respectively); (6) there was a significant association between age and IgE anti-RSV in non-asthma (P = 0.008), but not in asthma (P = 0.64). Our findings indicate that IgE-anti-RSV Ab responses may play important roles in RSV infection and asthma.     

Origin of CD8^＋ Effector and Memory T Cell Subsets

It is well accepted that CD8＋ T cells play a pivotal role in providing protection against infection with intracellular pathogens and some tumors. In many cases protective immunity is maintained for long periods of time （immunological memory）. Over the past years, it has become evident that in order to fulfill these multiple tasks, distinct subsets of effector and memory T cells have to be generated. Until today, however, little is known about the underlying mechanisms of subset differentiation and the timing of lineage fate decisions. In this context, it is of special importance to determine at which level of clonal expansion functional and phenotypical heterogeneity is achieved. Different models for T cell subset diversification have been proposed; these differ mainly in the time point during priming and clonal expansion （prior, during, or beyond the first cell division） when differentiation programs are induced. Recently developed single-cell adoptive transfer technology has allowed us to demonstrate that individual precursor cell still bears the full plasticity to develop into a plethora different T cell subsets. This observation targets the shaping of T cell subset differentiation towards factors that are still operative beyond the first cell division. These findings have important implications for vaccine development, as the modulation of differentiation patterns towards distinct subsets could become a powerful strategy to enhance the efficacy and quality of vaccines. Cellular ＆ Molecular Immunology.