Hammad H, de Vries V C, Maldonado-Lopez R, Moser M, Maliszewski C, Hoogsteden H C, Lambrecht B N
Department of Pulmonary Medicine, Erasmus Medical Center, 3015 GE Rotterdam, The Netherlands.
Clin Exp Allergy. 2004 Dec;34(12):1834-40. doi: 10.1111/j.1365-2222.2004.02133.x.
Different subsets of dendritic cells (DCs), identified in mouse spleen by their differential expression of CD8 alpha, can induce different T-helper (Th) responses after systemic administration. CD8 alpha(-) DCs have been shown to preferentially induce Th type 2 (Th2) responses whereas CD8 alpha(+) DCs induce Th1 responses.
To study if these DC subsets can still induce different Th responses in the Th2-prone milieu of the lung and differentially prime for eosinophilic airway inflammation, typical of asthma.
Donor mice first received daily Flt3L injections to expand DC numbers. Purified CD8 alpha(+) or CD8 alpha(-) splenic DCs were pulsed with ovalbumin (OVA) or phosphate-buffered saline and injected intratracheally into recipient mice in which carboxyfluorescein diacetate succinimidyl ester-labelled OVA-specific T cell receptor transgenic T cells had been injected intravenously 2 days earlier. T cell proliferation and cytokine production of Ag-specific T cells were evaluated in the mediastinal lymph nodes (MLNs) 4 days later. The capacity of both subsets of DCs, to prime for eosinophilic airway inflammation was determined by challenging the mice with OVA aerosol 10 days later.
CD8 alpha(-) DCs migrated to the MLN and induced a vigorous proliferative T cell response accompanied by high-level production of IL-4, IL-5, IL-10 and also IFN-gamma during the primary response and during challenge with aerosol, leading to eosinophilic airway inflammation. In the absence of migration to the MLN, CD8 alpha(+) DCs still induced a proliferative response with identical levels of IFN-gamma but reduced Th2 cytokines compared with CD8 alpha(-) DCs, which led to weak eosinophilic airway inflammation upon OVA aerosol challenge. Unpulsed DCs did not induce proliferation or cytokine production in Ag-specific T cells.
CD8 alpha(-) DCs are superior compared with CD8 alpha(+) DCs in inducing Th2 responses and eosinophilic airway inflammation in the Th2-prone environment of the lung.
通过树突状细胞（DC）表面CD8α的差异表达，可在小鼠脾脏中鉴定出不同的DC亚群，全身给药后它们可诱导不同的辅助性T细胞（Th）应答。已证实，CD8α阴性DC优先诱导2型Th（Th2）应答，而CD8α阳性DC诱导Th1应答。
研究在哮喘典型的、易发生Th2反应的肺部环境中，这些DC亚群是否仍能诱导不同的Th应答，并引发嗜酸性粒细胞性气道炎症。
供体小鼠首先每日注射Flt-3配体以增加DC数量。用卵清蛋白（OVA）或磷酸盐缓冲盐水对纯化的CD8α阳性或CD8α阴性脾DC进行脉冲处理，然后经气管内注射到受体小鼠体内，而在2天前已给受体小鼠静脉注射了羧基荧光素二乙酸琥珀酰亚胺酯标记的OVA特异性T细胞受体转基因T细胞。4天后，在纵隔淋巴结（MLN）中评估抗原特异性T细胞的增殖和细胞因子产生情况。10天后，用OVA气雾剂攻击小鼠，以确定这两种DC亚群引发嗜酸性粒细胞性气道炎症的能力。
CD8α阴性DC迁移至MLN，并在初次应答期间及气雾剂攻击时诱导强烈的T细胞增殖反应，同时高水平产生IL-4、IL-5、IL-10以及IFN-γ，从而导致嗜酸性粒细胞性气道炎症。在未迁移至MLN的情况下，CD8α阳性DC仍诱导增殖反应，IFN-γ水平与CD8α阴性DC相同，但Th2细胞因子水平低于CD8α阴性DC，这在OVA气雾剂攻击后导致较弱的嗜酸性粒细胞性气道炎症。未进行脉冲处理的DC未诱导抗原特异性T细胞增殖或产生细胞因子。
在肺部易发生Th2反应的环境中，与CD8α阳性DC相比，CD8α阴性DC在诱导Th2应答和嗜酸性粒细胞性气道炎症方面更具优势。
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