Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma.

Dose-dependent recruitment of CD25+ and CD26+ T cells in a novel F344 rat model of asthma.
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在新型 F344 大鼠哮喘模型中,CD25 和 CD26 T 细胞的剂量依赖性募集。

DOI:
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发表时间:
2007
期刊:
American Journal of Physiology - Lung cellular and Molecular Physiology
影响因子:
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通讯作者:
M. Stephan
M. Stephan
中科院分区:
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文献类型:
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作者:
T. Skripuletz;A. Schmiedl;Jutta Schade;S. Bedoui;T. Glaab;R. Pabst;S. von Hörsten;M. Stephan

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卵清蛋白(OVA)诱导的大鼠气道炎症是研究哮喘病理学的常用模型。然而,其敏感性在大鼠品系之间变化很大,目前优先使用Brown Norway(BN)大鼠。由于T细胞向肺的募集取决于CD 26(二肽基肽酶IV,DPPIV)表达,Fischer 344品系(F344)大鼠是高度相关的大鼠品系,特别是因为可获得CD 26缺陷型亚系。为建立F344大鼠哮喘模型,我们用不同剂量的雾化抗原(0%、1%、2.5%、5%和7.5% OVA)攻击F344大鼠,并将这些效果与OVA(1.5 mg/0.3 ml)气管内滴注进行比较。通过分析早期气道反应性(ERI)、抗原特异性IgE水平以及气道炎症(包括支气管肺泡灌洗液(BAL)和肺组织中T细胞亚群的组成,特别是T细胞活化标志物CD 25和CD 26)来确定哮喘反应性。即使是低剂量的过敏原也会引起过敏原特异性IgE水平的升高。然而,IgE和IgE水平未呈剂量依赖性增加。较高浓度的卵清蛋白导致过敏性哮喘的几种免疫学标志物的剂量依赖性增加,包括嗜酸性粒细胞、T细胞和树突状细胞的流入。有趣的是,在肺中发现了CD 4(+)/CD 25(+)/CD 26(+)T细胞的剂量依赖性增加。综上所述,我们建立了一种新的雾化OVA诱导的哮喘大鼠模型F344。因此,我们发现过敏性哮喘的细胞标志物包括活化的CD 4(+)/CD 25(+)/CD 26(+)T细胞亚群的剂量依赖性募集,这在哮喘中尚未描述。
The ovalbumin (OVA)-induced airway inflammation in rats is a commonly used model to explore the pathobiology of asthma. However, its susceptibility varies greatly between rat strains, and presently Brown Norway (BN) rats are preferentially used. Since recruitment of T cells to the lungs depends on the CD26 (dipeptidyl peptidase IV, DPPIV) expression, Fischer 344 strain (F344) rats are a highly relevant rat strain, in particular because CD26-deficient substrains are available. To establish a F344 rat model of asthma, we challenged F344 rats using different doses of aerosolized antigen (0%, 1%, 2.5%, 5%, and 7.5% OVA) and compared these effects with intratracheal instillation of OVA (1.5 mg/0.3 ml). Asthmoid responsiveness was determined by analysis of early airway responsiveness (EAR), antigen-specific IgE levels, as well as airway inflammation including the composition of T cell subpopulations in the bronchoalveolar lavage (BAL) and lung tissue with special respect to the T cell activation markers CD25 and CD26. Even low allergen doses caused allergen-specific EAR and increases of antigen-specific IgE levels. However, EAR and IgE levels did not increase dose dependently. Higher concentrations of OVA led to a dose-dependent increase of several immunological markers of allergic asthma including an influx of eosinophils, T cells, and dendritic cells. Interestingly, a dose-dependent increase of CD4(+)/CD25(+)/CD26(+) T cells was found in the lungs. Summarizing, we established a novel F344 rat model of aerosolized OVA-induced asthma. Thereby, we found a dose-dependent recruitment of cellular markers of allergic asthma including the activated CD4(+)/CD25(+)/CD26(+) T cell subpopulation, which has not been described in asthma yet.
DOI: 10.1165/ajrcmb.21.4.3659
发表时间: 1999-10-01
影响因子: 6.4
作者:
Hamelmann, E;Takeda, K;Gelfand, EW
通讯作者: Gelfand, EW
DOI: 10.1056/nejm199110103251504
发表时间: 1991-10-10
影响因子: 158.5
作者:
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通讯作者: HOLDAWAY, MD