肺树突状细胞亚群与哮喘Th2免疫反应

树突状细胞（dendritic cells,DCs）作为机体功能最强的专职抗原递呈细胞在过敏性哮喘的发生发展中起关键作用。近年发现肺DCs存在不同亚群,且在哮喘Th2免疫反应中发挥不同作用。CD11b＋经典树突状细胞（conventional dendritic cell,CD11b＋cDCs,cDC2s）是捕获致敏原并迁移至纵膈淋巴结将抗原提呈给CD4＋T细胞并诱导哮喘Th2免疫反应的主要DCs亚群,CD103＋经典树突状细胞（conventional dendritic cell,CD103＋cDCs,cDC1s）在哮喘Th2免疫反应中的作用存在争议,有不同研究发现cDC1s在哮喘Th2反应中起促进或抑制作用,浆细胞样树突状细胞（plasmacytoid dendritic cell,pDCs）与诱导气道免疫耐受有关,而单核细胞来源的DCs（monocyte-derived DCs,moDCs）通过分泌大量细胞因子在促进肺局部炎症中发挥重要作用,因此有必要就肺DCs亚群在过敏性哮喘Th2免疫反应中的作用作一综述。     

IRF-4结合蛋白——一个新的Th2极性分化相关分子

Th细胞的极性分化在免疫反应调控中具有重要作用,Th细胞极化失调所致Th1／Th2失衡与多种疾病的发生相关。对于细胞因子、抗原信号,转录因子等影响Th1／Th2分化倾向的相关调控因素的研究已比较深入,但分化的具体分子机制尚未完全阐明。IRF-4结合蛋白（IBP）是一个新发现的与Th活化及Th2极性分化相关的分子,它的发现为Th极化的分子机制的研究提供了新的线索。本文就IBP的发现及其在Th细胞极化中的作用做一综述。     

Th细胞分化调节机制研究进展

Th细胞可分化为Th1和Th2细胞亚群 ,分别介导细胞和体液免疫反应。本文从分子水平阐明Th细胞分化的调节机制 ,藉以了解其对许多疾病的治疗及对免疫病理反应干预的重要意义。     

胸腺基质淋巴生成素对树突状细胞的活化作用及其在Th2型炎症中的意义

树突状细胞(dendritic cells, DCs)是体内最重要的抗原提呈细胞,其对外源性抗原的高效的加工、处理和提呈是启动T细胞应答的关键步骤;同时DCs又是免疫应答的重要调节者,不同微环境中的DCs受不同因子的作用而发生不同的成熟活化过程,从而诱导机体产生针对该环境所需要的不同的免疫应答.胸腺基质淋巴生成素(Thymic stromal lymphopoietin,TSLP)是一类优先表达于肺、肠、皮肤等上皮细胞的细胞因子,尤其在超敏反应性炎症部位表达极高.TSLP对DCs具有重要调控作用,可促进DCs的活化、成熟,增强其对CD4 T细胞的活化能力,并促使Th0细胞向Th2分化,在特应性皮炎、哮喘等炎症发生中具有重要意义.     

树突状细胞、Th2细胞和调节性T细胞在哮喘中的作用

目前树突状细胞(DC)被认为是最重要的专职抗原递呈细胞，并且在刺激初始CD^4 T细胞向Th2细胞分化中发挥重要的作用，它可以导致Th2／Th1比例失调从而引起变应性哮喘。近些年来，人们认识到DC在变应性哮喘的发生、发展、持续中起着重要的作用，本文拟就有关内容作一综述。     

017 Th1/Th2和Tc1/Tc2与慢性丙型肝炎

CD4+T细胞根据分泌的细胞因子不同可分为Th1和Th2细胞,同样,分泌Th1和分泌Th2样细胞因子的CD8+T细胞分别命名为Tc1和Tc2.一般说来,Th1细胞促进细胞免疫反应,Th2细胞促进体液免疫反应.Th1/Th2以及Tc1/Tc2细胞失衡与丙型肝炎的发病有密切的相关性,本文就这方面的有关研究近况作一简述.     

Th1/Th2和Tc1/Tc2与慢性丙型肝炎

CD4 +T细胞根据分泌的细胞因子不同可分为Th1和Th2细胞 ,同样 ,分泌Th1和分泌Th2样细胞因子的CD8+T细胞分别命名为Tc1和Tc2。一般说来 ,Th1细胞促进细胞免疫反应 ,Th2细胞促进体液免疫反应。Th1/Th2以及Tc1/Tc2细胞失衡与丙型肝炎的发病有密切的相关性 ,本文就这方面的有关研究近况作一简述。     

Th1／Th2与慢性乙型肝炎

慢性乙型肝炎发病机制复杂，与机体的免疫状态密切相关，CD4^ Th细胞是机体的重要调节细胞，根据其产生细胞因子的不同分为Th1和Th2亚型，分别参与调节细胞免疫和体液免疫，Th1和Th2可相互调节，影响免疫应答的格局，Th1／Th2在多种感染性疾病中发挥重要作用，慢性乙肝患者存在Th1／Th2失衡，本文就Th1／Th2与慢性乙肝的关系研究进展进行简述。     

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。     

树突状细胞、Th2细胞和调节性T细胞在哮喘中的作用

目前树突状细胞 (DC)被认为是最重要的专职抗原递呈细胞 ,并且在刺激初始CD4 + T细胞向Th2细胞分化中发挥重要的作用 ,它可以导致Th2 /Th1比例失调从而引起变应性哮喘。近些年来 ,人们认识到DC在变应性哮喘的发生、发展、持续中起着重要的作用 ,本文拟就有关内容作一综述。     

Human dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B cells from atopic individuals in vitro

Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4(+) T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-gamma (IFN-gamma)-producing CD8(+) T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human monocyte-derived DC from grass-pollen allergic donors were transfected with an adenovirus encoding the allergen Phleum pratense 1 and cocultured with B cells, autologous CD4(+) T cells, and CD40 ligand-transfected L-cells. B cells receiving help from CD4(+) T cells stimulated with allergen-transfected dendritic cells produced more allergen-specific IgG4 compared to stimulation with allergen protein pulsed DC or medium, while total IgG4 production was not affected. In contrast, specific IgE production was not enhanced by stimulation with allergen-DNA transfected DC compared to medium and inhibited compared to allergen protein-pulsed DC with similar effects on total IgE production in vitro. Allergen-DNA transfected dendritic cells are able to direct the human allergic immune response from Th2-dominance towards Th1 and Tc1 also resulting in decreased IgE and increased IgG4 production.     

The interplay of dendritic cells, Th2 cells and regulatory T cells in asthma

Dendritic cells are essential for Th2 differentiation of naive CD4+ T cells in response to aeroallergens, and in recent years it has been well established that these cells play a pivotal role in the initiation phase of allergic asthma. Dendritic cells are also crucial for maintaining eosinophilic airway inflammation by controlling the recruitment and activation of primed Th2 cells in the lung. A picture is emerging wherein the balance of pathogenic Th2 cells and regulatory T cells is tuned by dendritic cells not only at the initiation but also at the effector stage of the allergic immune response.     

Cytotoxic T lymphocyte antigen 4 immunoglobulin modified dendritic cells attenuate allergic airway inflammation and hyperresponsiveness by regulating the development of T helper type 1 (Th1)/Th2 and Th2/regulatory T cell subsets in a murine model of asthma

T helper type 2 (Th2) and regulatory T cells (T(reg) ) have been postulated to have critical roles in the pathogenesis of allergic asthma. Cytotoxic T lymphocyte antigen 4 immunoglobulin (CTLA4Ig) gene-modified dendritic cells (DC-CTLA4Ig) have the potential to reduce Th2 cells and induce T(reg) cells. In the present study, we evaluated the therapeutic effects and potential mechanisms of the adoptive transfer of DC-CTLA4Ig into mice in an experimental model of asthma. BALB/c mice were sensitized with ovalbumin (OVA) and challenged with aerosolized OVA for 7 days. Just prior to the first challenge, DC-CTLA4Ig, DCs or DCs infected with DC-green fluorescent protein (GFP) were injected intravenously into mice. The administration of DC-CTLA4Ig reduced airway hyperresponsiveness, relieved asthmatic airway inflammation and decreased the numbers of esosinophils in the BALF in OVA-sensitized/challenged mice. In addition, DC-CTLA4Ig altered the balance of Th1/Th2 cytokine production in the lungs with increased interferon (IFN)-γ levels and decreased interleukin (IL)-4 levels, decreased the percentage of Th2 and increased both the percentage of Th1 and T(reg) cells in the lungs of OVA-sensitized/challenged mice. This research demonstrates that DC-CTL4Ig reduces airway hyperresponsiveness effectively and prevents airway inflammation in OVA-sensitized/challenged mice, which is due most probably to attenuated secretion of Th2 cytokines and increased secretion of Th1 cytokines in the local airway, and the correction of the pulmonary imbalance between Th1/Th2 cells and Th2/T(reg) cells.     

Prostatein or steroid binding protein (PSBP) induces experimental autoimmune prostatitis (EAP) in NOD mice

Antigen-pulsed dendritic cells (DCs) have been used extensively as cellular vaccines to induce a myriad of protective immune responses. Adoptive transfer of antigen-pulsed DCs is especially effective at generating Th1 and CD8 immune responses. However, recently this strategy has been shown to induce Th2 cells when DCs are administered locally into the respiratory tract. We sought to address whether systemic rather than local antigen-pulsed DC administration could induce Th2 experimental allergic asthma. We found that OVA-pulsed splenic DCs injected intraperitoneally induced polarized Th2 allergic lung disease upon secondary OVA aerosol challenge. Disease was characterized by eosinophilic lung inflammation, excess mucus production, airway hyperresponsiveness, and OVA-specific IgG1 and IgE. In addition, unusual pathology characterized by macrophage alveolitis and multinucleated giant cells was observed. These data show that systemic administration of antigen-pulsed DCs and subsequent aeroantigen challenge induces Th2 immunity. These findings have important implications for the development of DC-based vaccines.     

Differential control of CD4+ T‐cell subsets by the PD‐1/PD‐L1 axis in a mouse model of allergic asthma

Studies examining the role of PD‐1 family members in allergic asthma have yielded conflicting results. Using a mouse model of allergic asthma, we demonstrate that blockade of PD‐1/PD‐L1 has distinct influences on different CD4⁺ T‐cell subsets. PD‐1/PD‐L1 blockade enhances airway hyperreactivity (AHR), not by altering the magnitude of the underlying Th2‐type immune response, but by allowing the development of a concomitant Th17‐type immune response. Supporting differential CD4⁺ T‐cell responsiveness to PD‐1‐mediated inhibition, naïve PD‐1^?/? mice displayed elevated Th1 and Th17 levels, but diminished Th2 cytokine levels, and ligation of PD‐1 in WT cells limited cytokine production by in vitro polarized Th1 and Th17 cells, but slightly enhanced cytokine production by in vitro polarized Th2 cells. Furthermore, PD‐1 ligation enhanced Th2 cytokine production by naïve T cells cultured under nonpolarizing conditions. These data demonstrate that different CD4⁺ T‐cell subsets respond differentially to PD‐1 ligation and may explain some of the variable results observed in control of allergic asthma by the PD‐1 family members. As the PD‐1/PD‐L1 axis limits asthma severity by constraining Th17 cell activity, this suggests that severe allergic asthma may be associated with a defective PD‐1/PD‐L1 regulatory axis in some individuals.     

Role of regulatory dendritic cells in allergy and asthma

PURPOSE OF REVIEW: Dendritic cells are the most efficient inducers of all immune responses, and are capable of inducing either productive immunity or maintaining the state of tolerance to self-antigens and allergens. The present review summarizes the emerging literature on dendritic cells, with the emphasis on regulatory function of dendritic cells in allergy and asthma. In particular we summarize recent data regarding the relationship between dendritic cell subsets and Th1, Th2 and regulatory T (TReg) cells. RECENT FINDINGS: The diverse functions of dendritic cells have been attributed to distinct lineages of dendritic cells, which arise from common immature precursor cells that differentiate in response to specific maturation-inducing or local microenvironment conditions. These subsets induce different lineages of T cells such as Th1, Th2 and TReg cells, including Th1Reg and Th2Reg cells, which regulate allergic diseases and asthma. SUMMARY: Subsets of dendritic cells regulate the induction of a variety of T-cell subtypes, which suppress the development of allergy and asthma, thus providing antiinflammatory responses and protective immunity.     

嗜碱性粒细胞对Th2细胞免疫应答调节的研究进展

嗜碱性粒细胞是外周循环中比例最少的一类粒细胞,早期研究认为其是蠕虫感染应答和过敏性炎症的主要效应细胞.近年来,大量研究证明嗜碱性粒细胞密切参与Th2细胞免疫应答生成,主要通过分泌IL-4,作为抗原提呈细胞以及与树突状细胞协同作用三种方式参与调节Th2细胞免疫应答.在不同类型抗原引起的Th2细胞免疫应答中,嗜碱性粒细胞发挥的作用也不尽相同.     

Innate and adaptive type 2 immunity in lung allergic inflammation

Allergic inflammation is a type 2 immune disorder classically characterized by high levels of immunoglobulin E (IgE) and the development of Th2 cells. Asthma is a pulmonary allergic inflammatory disease resulting in bronchial hyper-reactivity. Atopic asthma is defined by IgE antibody-mediated mast cell degranulation, while in non-atopic asthma there is no allergen-specific IgE and more involvement of innate immune cells, such as basophils, group 2 innate lymphoid cells (ILC2), and eosinophils. Recently, protease allergens were shown to cause asthmatic responses in the absence of Th2 cells, suggesting that an innate cell network (IL-33/TSLP-basophil-ILC2-IL-5/IL-13 axis) can facilitate the sensitization phase of type 2 inflammatory responses. Recent evidence also indicates that in the chronic phase, these innate immune cells directly or indirectly contribute to the adaptive Th2 cell responses. In this review, we discuss the role of Th2 cytokines (IL-4 and IL-13) and innate immune cells (mast cells, basophils, ILC2s, and dendritic cells) in the cross-talk between innate and adaptive inflammatory responses.     

Allergen uptake and presentation by dendritic cells

Allergic diseases such as atopic dermatitis, rhinitis and asthma are thought to result from a dysregulated immune response to commonly encountered antigens in genetically predisposed individuals. This response leads to chronic eosinophil-rich allergic inflammation and is controlled by Th2 lymphocytes. The first step in the allergic immune response is the uptake and presentation of allergen by professional antigen presenting cells such as dendritic cells, macrophages and B lymphocytes. Immature dendritic cells reside in the epithelia of the skin, upper and lower airways and gut and have the potential to sense foreign antigens and non-specific inflammatory tissue damage. Following recognition and uptake of Ag, mature dendritic cells migrate to the T-cell rich area of draining lymph nodes, display an array of Ag-derived peptides on the surface of major histocompatibility complex molecules and acquire the cellular specialization to select and activate naive Ag-specific T cells. By the nature of the signals they provide to naive T cells, mature dendritic cells are critical for polarizing Th0 helper cells into either Th1 or Th2 effector cells and for inducing long-lived memory Th cells. This article reviews recent information implying dendritic cells in the pathogenesis of allergic disease.