支气管哮喘与免疫调节

支气管哮喘（哮喘）是由环境过敏原引起基因易感人群Th1／Th2免疫失衡,Th2功能亢进而引起的。产生Th2细胞因子的CD4^＋T细胞在哮喘发生过程中起了关键的作用。各种特异性致炎因子,调节性T细胞,抗原递呈细胞以及免疫球蛋白都参与了哮喘的发生,本文就哮喘与免疫调节的关系以及免疫治疗的前景作一综述。     

白细胞介素-27在支气管哮喘发病中的作用

支气管哮喘(简称哮喘)的发病机制与辅助性T细胞(Th)亚群Th1/Th2细胞免疫应答失衡密切相关,T细胞及其细胞因子在哮喘病理过程中起着至关重要的作用.     

过敏性支气管哮喘免疫发病机制的最新研究进展

过敏性支气管哮喘(简称哮喘)是一种由不同的辅助性T细胞亚型决定的慢性气道炎症性疾病.既往认为“Th2哮喘假说”是过敏性哮喘的主要发病机制,而越来越多的研究表明,除了Th2之外其他辅助性T细胞也参与了哮喘的发病机制,尤其是Th1和Th17细胞对于气道中性粒细胞型炎症的发展至关重要.抑制这些免疫细胞也许为过敏性哮喘的有效治疗提供了方向.     

CD4+T细胞与支气管哮喘治疗研究新进展

在支气管哮喘(简称哮喘)中,Th2细胞及其细胞因子促使气道嗜酸粒细胞炎症浸润和气道高反应产生,是哮喘治疗的重要靶点.越来越多的研究结果显示,除Th2细胞外,其他CD4+T细胞[包括Th1、Th17及调节性T细胞(Treg)]也可以被招募至气道,共同参与哮喘发病.哮喘的免疫学治疗复杂,现将各亚群CD4+T细胞在哮喘治疗中的研究进展综述如下.     

荷瘤小鼠髓系来源抑制性细胞对CD8+ CD28-T细胞的调控及其在支气管哮喘中的作用

目前国内外支气管哮喘(简称哮喘)的患病率和病死率逐渐上升,已成为严重威胁人们健康的主要慢性疾病,Th1/Th2平衡理论一直作为哮喘发病机制的核心.近年来研究结果表明,除Th1和Th2细胞外,还存在一种调节性T细胞(Tr),其中CD8+调节性T细胞( CD8+ Tr)是发挥抑制作用的效应细胞[1]. 髓系来源抑制性细胞( MDSC)为近来研究发现在肿瘤患者体内聚积的一类与肿瘤免疫逃逸密切相关的髓样细胞,其由不同分化阶段的髓系细胞组成.Huang等[2]研究发现MDSC能在荷瘤小鼠体内上调CD4+、CD8+ Tr的比例,引起免疫无能和抑制.     

香烟烟雾暴露对支气管哮喘大鼠OX-62蛋白和白细胞介素12表达的影响

吸烟不仅可引起支气管哮喘(简称哮喘)频繁发作,导致肺功能迅速下降,而且可以降低糖皮质激素的治疗效果,最终使病情不易控制[1-2].树突状细胞(dendritic cell,DC)是功能最强的抗原提呈细胞(APC),可以产生调节辅助性T细胞1(Th1)/Th2平衡的关键细胞因子--白细胞介素(IL)-12,并在哮喘和过敏性疾病中发挥重要作用.本研究中拟探讨香烟烟雾暴露对哮喘大鼠肺部DC的特异性标记蛋白OX-62以及血浆和BALF中IL-12表达的影响,以期阐述吸烟加重哮喘的免疫调节机制.     

影响支气管哮喘Th1/Th2失衡的因素及治疗的新视点

支气管哮喘(简称哮喘)是由嗜酸粒细胞、肥大细胞和T细胞等多种炎性细胞参与的气道慢性炎症性疾病,其发病机制极为复杂,近来研究发现Th1/Th2失衡是哮喘免疫学发病机制中的一个重要环节,本文就Th1/Th2失衡与哮喘的关系,Th1/Th2平衡的调节及其在哮喘治疗中的价值作一综述.     

T细胞在哮喘免疫调节中的作用

哮喘是由T细胞、嗜酸粒细胞、肥大细胞等多种炎症细胞参与的气道慢性炎症性疾病,气道慢性炎症导致气道高反应性(AHR)的形成。其中Th2细胞通过分泌IL-4、IL-5、IL-9、IL-13等多种细胞因子在哮喘发病中起主要作用,而Th1分泌的IFN-γ抑制Th2的功能,近年来研究发现CD4+T细胞还包括多种具有调节功能的细胞群体并参与哮喘的免疫调节。另外,NKT细胞和CD8+T细胞在哮喘免疫调节中亦具有一定的作用。1Th1/Th2与哮喘1986年,Mossmann等[1]发现小鼠CD4+T存在Th1和Th2两个亚群,Th1产生白介素-2(IL-2)、干扰素(IFN)γ和β,不产生IL-4和IL…     

共刺激信号与支气管哮喘γδT细胞活化关系的研究

我们之前的研究表明[1,2],γδ T细胞在哮喘支气管肺泡灌洗液(BALF)中明显活化;γδ T细胞可能存在Th1/Th2模式,并表现为Th2样优势应答.为进一步阐明γδ T细胞活化的细胞和分子机制,我们探讨了单核/巨噬细胞(Mon/Mφ)与γδ T细胞间共刺激分子B7∶CD28/CTLA-4( )的改变.材料与方法 2～3月龄雄性Wistar大鼠20只,体重(200±50)g.随机分正常组和哮喘组,每组各10只.哮喘模型的建立、鉴定及标本的收集和处理按方法[1].     

γδT细胞与支气管哮喘关系的研究进展

支气管哮喘（哮喘）是以气道嗜酸粒细胞、淋巴细胞等炎症细胞浸润为主、气道高反应性增高为特征、Th1/Th2反应失衡并表现为Th2优势应答的疾病.关于淋巴细胞与哮喘的关系大部分研究仅限于αβT细胞,对γδT细胞在支气管哮喘发生发展中的作用是近十多年来才开始关注的.本文就γδT细胞的免疫学特性及与哮喘的关系作一综述.     

Group 2 innate lymphoid cells in human asthma

Asthma is characterized by increased airway hyperresponsiveness, reversible airflow limitation, and remodeling due to allergic airway inflammation. Asthma has been proposed to be classified into various phenotypes by cluster analyses integrating clinical information and laboratory data. Recently, asthma has been classified into two major endotypes, Type 2-high and Type 2-low asthma, and various subtypes based on the underlying molecular mechanisms. In Type 2-high asthma, Th2 cells, together with group 2 innate lymphoid cells (ILC2s), produce type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13, which play crucial roles in causing airway inflammation. The roles of ILC2s in asthma pathogenesis have been analyzed primarily in murine models, demonstrating their importance not only in IL-33- or papain-induced innate asthma models but also in house dust mite (HDM)- or ovalbumin (OVA)-induced acquired asthma models evoked in an antigen-specific manner. Recently, evidence regarding the roles of ILC2s in human asthma is also accumulating. This minireview summarizes the roles of ILC2s in asthma, emphasizing human studies.     

Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation

Asthma is the most prevalent allergic disease of the airway, which is characterized by eosinophilic inflammation, mucus hyperproduction, and airway hyper-responsiveness. Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma. IL-22, one of the cytokines produced by Th17 cells and type 3 ILCs, has distinct functional properties, as IL-22 exclusively acts on non-hematopoietic cells including epithelial cells of mucosal surface and exhibits a broad range of action in regeneration and host protection. In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation. In this review, we discuss recent advances in the biology of IL-22 and its involvement in the pathogenesis of allergic airway inflammation.     

Alteration of balance between myeloid dendritic cells and plasmacytoid dendritic cells in peripheral blood of patients with asthma

Asthma, a well-known helper T cell Type 2 (Th2)-mediated disease, has a polarized immune response toward a Th2 phenotype. However, the factors causing the Th2 polarization remain to be fully determined in this disease. Dendritic cells (DCs) are the most potent antigen-presenting cells that play a central role in initiating the primary immune response. In human blood, two functional distinct subsets of DCs, myeloid DCs and plasmacytoid DCs, have been identified. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) are also called Type 1 DCs (DC1) and Type 2 DCs (DC2), respectively, because mDCs and pDCs were shown to preferentially differentiate naive T cells into Th1 and Th2 cells, respectively. In asthma, it can thus be speculated that an altered balance of mDCs to pDCs toward pDCs may contribute to the Th2 polarization. To clarify this, we examined the numbers of mDCs and pDCs in the peripheral blood of 44 patients with asthma and 38 normal subjects, using multicolor flow cytometry. We found that the patients with asthma had a significantly higher number of pDCs, resulting in a significant decrease in the ratio of mDCs to pDCs compared with normal subjects. These data indicate that the patients with asthma had a polarization of the mDC:pDC balance toward pDCs, which may be involved in producing the Th2-dominant immune phenotype in asthma.     

CpG-寡核苷酸与支气管哮喘

Th1／Th2失衡是支气管哮喘的重要免疫学发病机制,近年在支气管哮喘的发病机制中取得较大进展,CD4^＋T辅助细胞按其分泌的细胞因子不同分为Th1和Th2细胞,Th1反应可以抑制Th2反应,抑制气遭慢性炎症,含有未甲基化CpG结构的寡核苷酸是近年研究较多的一种调节Th1／Th2平衡的免疫制剂,本文就其调节Th1／Th2平衡在支气管哮喘治疗中的应用前景作一综述。     

Control of T helper 2 cell function and allergic airway inflammation by PKCzeta

Asthma is a disease of chronic airway inflammation in which T helper (Th) 2 cells play a critical role. The molecular mechanisms controlling Th2 differentiation and function are of paramount importance in biology and immunology. PKCzeta has been implicated in the regulation of apoptosis and NF-kappaB, as well as in the control of T-dependent responses, although no defects were detected in na?ve T cells from PKCzeta-/- mice. Here, we report that PKCzeta is critical for IL-4 signaling and Th2 differentiation. Thus, PKCzeta levels are increased during Th2 differentiation, but not Th1 differentiation, of CD4+ T cells, and the loss of PKCzeta impairs the secretion of Th2 cytokines in vitro and in vivo, as well as the nuclear translocation and tyrosine phosphorylation of Stat6 and Jak1 activation, essential downstream targets of IL-4 signaling. Moreover, PKCzeta-/- mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKCzeta can be a therapeutic target in asthma.     

Immunopathologie de l'asthme sévère

Severe asthma represents a heterogeneous entity for which the immunopathology is poorly understood, in part because of the difficulty of obtaining material in situ material from patients. There are two types of severe asthma, depending on the presence or absence of eosinophils. The pathophysiology of severe asthma of early onset with eosinophilia is similar to that of less severe asthma, with infiltration of Th2 lymphocytes; such cases are more likely to have exacerbations. When the onset occurs later, asthma is much more like the hypereosinophilic syndromes. Severe asthma without eosinophilia is more often accompanied by neutrophil infiltration; this type of asthma responds poorly to corticoids. Induced sputum can be used for non-invasive longitudinal follow-up of bronchial inflammation in severe asthma, allowing evaluation of cellular activation during and between exacerbations. The ISEA study (Induced Sputum in Exacerbations of Asthma) revealed that simultaneous activation of Th1 and Th2 lymphocytes and a greater deficiency of T regulatory lymphocytes occur during the course of exacerbations. This type of approach is indispensable for the identification of relevant therapeutic targets, and ultimately for the identification of early markers that are predictive of exacerbations.     

Toll样受体、CD4+CD25+调节性T细胞与支气管哮喘的关系

Toll样受体（TLR）是机体识别环境中各种微生物的主要受体，是介导天然免疫和获得性免疫的桥梁。支气管哮喘（哮喘）的发病是环境和基因相互作用的结果，TLR与哮喘有着十分密切的关系。近年来，人们逐渐认识到Th1／Th2理论并不能充分阐明哮喘的发病机制。随着对哮喘的深入研究，CD4^＋CD25^＋调节性T细胞凸现其冰山一角。本文就近年来对TLR、CD4^＋CD25^＋调节性T细胞和哮喘关系的研究进展作一综述。     

白介素4在支气管哮喘发病机制中的作用及其靶向治疗研究

支气管哮喘（简称哮喘）发病率正逐年上升,其发病机制十分复杂。目前认为Th1/Th2反应失衡导致Th2细胞增多是其重要的发病机制之一,其中Th2细胞产生的细胞因子白介素4在哮喘发病中起重要的作用,成为新的哮喘治疗靶点。     

Immune response to hepatitis B vaccine in asthmatic children

Asthma is a disease that demonstrates chronic Th2 lymphocyte-mediated pulmonary inflammation. We hypothesized that cytokines produced by asthmatic lung inflammation bias the immune response to antigens administered systemically toward a Th2 response, as assessed by serum IgE antibody and lymphocyte-secreted IL-4 and IL-5. We also hypothesized that treatment of asthmatic children with local anti-inflammatory agents reduces this cytokine-mediated Th2 influence. We systemically immunized groups of asthmatic children (n=29) who were participating in a long-term, randomized, placebo-controlled clinical trial of inhaled anti-inflammatory therapy (Childhood Asthma Management Program) and nonasthmatic children (n=12) with hepatitis B (Hep B) antigen, and examined their antigen-specific antibody and lymphocyte cytokine secretion profiles. The asthmatic population demonstrated an increased amount of Th2-mediated serum IgE anti-Hep B antibody, as compared to nonasthmatic children; but comparable amounts of IgG1, IgG2, IgG3, IgA, and IgM anti-Hep B antibody and lymphocyte IFNgamma, IL4, and IL5. There was no significant difference of antibody isotype or cytokine production between asthmatic subjects receiving treatment with budesonide or nedocromil, as compared to placebo. In conclusion, there is a subtle bias in responses to systemic immunization in children with asthma, but anti-inflammatory therapy does not affect this bias. The findings support the concept that the Th2 bias may be largely genetic. Importantly, we confirmed that children with asthma, including even those on inhaled corticosteroids, responded to Hep B immunization as well as did nonasthmatic children with the major isotypes of anti-Hep B antibody, suggesting that vaccine protection against hepatitis B is not influenced by inhaled steroid therapy.