Comparative Analysis of Steroid Sensitivity of T Helper Cells in vitro and in vivo
Comparative Analysis of Steroid Sensitivity of T Helper Cells in vitro and in vivo
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DOI：
10.1159/000327494
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发表时间：
2011-01-01
影响因子：
2.8
通讯作者：
Mori, Akio
中科院分区：
文献类型：
--
作者：
Abe, Akemi;Ohtomo, Takayuki;Mori, Akio
背景：糖皮质激素（GC）对哮喘的作用部分被解释为抑制T细胞活化。我们分析了激素敏感性卵清蛋白（OVA）反应性辅助性T（Th）细胞克隆在体外和体内。方法：体外实验中，Th细胞克隆与抗原提呈细胞、卵清蛋白（OVA）和不同浓度的地塞米松（DEX）共同培养。通过3 H-胸苷摄取来测量每个Th克隆的增殖反应。对于体内实验，未致敏的BALB/c小鼠用Th克隆转移，用OVA攻击，并皮下施用DEX。测定支气管肺泡灌洗液（BALF）中浸润细胞数。结果如下：根据GC对体外增殖反应的影响，6个Th克隆被归类为类固醇敏感或类固醇抗性克隆。地塞米松能有效地抑制激素敏感克隆小鼠气道嗜酸性粒细胞和淋巴细胞的浸润。与此相反，与类固醇耐药克隆转移的小鼠的地塞米松没有显着抑制;嗜酸性粒细胞的数量在BALF中的小鼠转移1类固醇耐药克隆，即T5-1，仅部分减少。结论：体外测定的Th克隆的类固醇敏感性与体内测定的过继转移哮喘模型的一致。激素敏感型和激素抵抗型哮喘模型对于了解重度哮喘激素抵抗的机制具有重要意义。版权所有（C）2011 S. Karger AG，巴塞尔
Background: Glucocorticoid (GC) action on asthma has been partly explained by the inhibition of T cell activation. We analyzed the steroid sensitivity of ovalbumin (OVA) reactive helper T (Th) cell clones both in vitro and in vivo. Method: For in vitro experiments, Th clones were cultured with antigen-presenting cells, OVA, and various concentrations of dexamethasone (DEX). The proliferative response of each Th clone was measured by 3 H-thymidine uptake. For in vivo experiments, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered DEX subcutaneously. The number of infiltrating cells in bronchoalveolar lavage fluid (BALF) was measured. Results: Six Th clones were classified as steroid-sensitive or steroid-resistant clones in terms of the effects of GC on the proliferative responses analyzed in vitro. Airway infiltration of eosinophils and lymphocytes of mice transferred with steroid-sensitive clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with steroid-resistant clones were not significantly inhibited by DEX; the number of eosinophils in the BALF of mice transferred with 1 steroidresistant clone, i.e. T5-1, was only partially reduced. Conclusion: The steroid sensitivity of Th clones measured in vitro was consistent with that of an adoptively transferred asthma model measured in vivo. Steroid-sensitive and resistant asthma models seem valuable for understanding the mechanisms of steroid resistance in severe asthma. Copyright (C) 2011 S. Karger AG, Basel