Kushwah Rahul, Hu Jim
Stem Cell and Cancer Research Institute, McMaster University, Hamilton.
J Vis Exp. 2012 Jul 23(65):e4014. doi: 10.3791/4014.
Dendritic cells (DCs) are the key players involved in initiation of adaptive immune response by activating antigen-specific T cells. DCs are present in peripheral tissues in steady state; however in response to antigen stimulation, DCs take up the antigen and rapidly migrate to the draining lymph nodes where they initiate T cell response against the antigen. Additionally, DCs also play a key role in initiating autoimmune as well as allergic immune response. DCs play an essential role in both initiation of immune response and induction of tolerance in the setting of lung environment. Lung environment is largely tolerogenic, owing to the exposure to vast array of environmental antigens. However, in some individuals there is a break in tolerance, which leads to induction of allergy and asthma. In this study, we describe a strategy, which can be used to monitor airway DC maturation and migration in response to the antigen used for sensitization. The measurement of airway DC maturation and migration allows for assessment of the kinetics of immune response during airway allergic inflammation and also assists in understanding the magnitude of the subsequent immune response along with the underlying mechanisms. Our strategy is based on the use of ovalbumin as a sensitizing agent. Ovalbumin-induced allergic asthma is a widely used model to reproduce the airway eosinophilia, pulmonary inflammation and elevated IgE levels found during asthma. After sensitization, mice are challenged by intranasal delivery of FITC labeled ovalbumin, which allows for specific labeling of airway DCs which uptake ovalbumin. Next, using several DC specific markers, we can assess the maturation of these DCs and can also assess their migration to the draining lymph nodes by employing flow cytometry.
树突状细胞(DCs)是通过激活抗原特异性T细胞来启动适应性免疫反应的关键参与者。DCs在稳态下存在于外周组织中;然而,在抗原刺激下,DCs摄取抗原并迅速迁移至引流淋巴结,在那里它们启动针对该抗原的T细胞反应。此外,DCs在引发自身免疫以及过敏性免疫反应中也发挥关键作用。在肺部环境中,DCs在免疫反应的启动和耐受性的诱导方面都起着至关重要的作用。由于接触大量的环境抗原,肺部环境在很大程度上具有耐受性。然而,在一些个体中,耐受性会被打破,从而导致过敏和哮喘的诱发。在本研究中,我们描述了一种策略,可用于监测气道DCs在对用于致敏的抗原作出反应时的成熟和迁移情况。气道DCs成熟和迁移的测量有助于评估气道过敏性炎症期间免疫反应的动力学,也有助于理解后续免疫反应的程度及其潜在机制。我们的策略基于使用卵清蛋白作为致敏剂。卵清蛋白诱导的过敏性哮喘是一种广泛使用的模型,用于重现哮喘期间出现的气道嗜酸性粒细胞增多、肺部炎症和IgE水平升高的情况。致敏后,通过鼻内给予异硫氰酸荧光素(FITC)标记的卵清蛋白对小鼠进行激发,这使得摄取卵清蛋白的气道DCs能够被特异性标记。接下来,使用几种DC特异性标志物,我们可以评估这些DCs的成熟情况,还可以通过流式细胞术评估它们向引流淋巴结的迁移情况。