探討介白質10與介白質12基因對免疫細胞的調節與對OVA致敏氣喘小鼠的影響

The modulatory effect of IL-10 and IL-12 genes on immune cells and OVA-induced asthmatic mice

蘇筱喬(Hsiao-Chiao Su)

指導教授 ： 李岳倫助理教授

臺北醫學大學/醫學院/醫學科學研究所/碩士(2008年)

https://doi.org/10.6831/TMU.2008.00118

摘要

目前已知細胞激素IL-10可抑制Th1與Th2的細胞反應，而細胞激素IL-12則會誘發T細胞分化成Th1細胞並分泌IFN-γ來抑制Th2細胞的免疫反應。首先為探討IL-10及IL-12調控T細胞分化的影響，因此在細胞實驗實驗中我們藉由利用腺病毒載體攜帶IL-10 (Ad-IL-10)或IL-12 (Ad-IL-12)的基因感染由小鼠骨髓細胞分化的樹突細胞，而給予合併Ad-IL-10/IL-12所感染的樹突細胞，其細胞表面分子CD 80、CD 86與 MHC II的表現量會增加。將此修飾過的樹突細胞與CD4+ T細胞共同培養兩個循環後發現會誘發一群分泌高量IL-10與 IFN-γ的T細胞群，將此群的T細胞與作用型T細胞共同培養則此群Th1-like的T細胞具有抑制作用型T細胞增生的能力，若利用transwell隔離此兩種T細胞則發現此群T細胞主要是經由細胞與細胞間的接觸來達到對作用型T細胞的抑制效果，而非藉由所分泌IL-10來完全抑制作用T細胞的增生。
　　此外，我們進一步探討在氣喘動物模式下合併給予不同劑量的Ad-IL-10及Ad-IL-12感染的樹突細胞是否能夠有效的預防或改善氣喘發病的嚴重性。而由實驗結果發現：合併給予Ad-IL-10與Ad-IL-12感染的樹突細胞在預防與治療氣喘動物實驗中皆能有效的降低呼吸道阻力、肺部發炎細胞浸潤以及減少Th2細胞激素IL-4、IL-5與IL-13的分泌。所以結論為合併給予腺病毒載體 (Ad-IL-10/Ad-IL-12)的樹突細胞的確可以誘發動物體內產生一群特殊的Th1-like的調節型T細胞，並藉由所產生的細胞激素IFN-γ以及IL-10來抑制Th2的過度增生，而能有效的降低氣喘的發生以及改善發病的嚴重性；因此，將來利用此修飾的樹突細胞來進行對過敏疾病的治療可能不失為一更適合的治療方式。

關鍵字

介白質10 ； 介白質12 ； 免疫 ； 氣喘

並列摘要

The T helper type 2 cells (Th2) play a curial role in the initiation of allergic asthma. Asthma is characterized by reversible airway obstruction, eosinophilic infiltration, airway remodeling, mucus hypersecretion and airway hyperresponsiveness. In our studies, we use IL-10 or IL-12 expessing adenoviral vector to observe whether combination treatment can suppress the airway inflammation of allergic asthma. Firstly, we applied the Ad-IL-10/IL-12 to the bone marrow derived dendritic cells (DCs) and found such modified DCs expressed increased surface makers of CD 80, CD 86 and MHC class II. These modified DCs drived activated CD4+ T cells to differiate to specific T cell line. These special T cells secreted high levels of IL-10 and IFN-γ and suppressed the proliferation of effector T cells through cell-cell contact rather than the cytokine mediation. In the in vivo experiments, Ad-IL-10/IL-12 infected DCs were injected into OVA-induced asthmatic animal model to investigate whether modified DCs could prevent the development of asthma. The data showed that modified DCs suppressed the development of airway hyper-responsiveness, reduced airway inflammation and enhanced the expression of IL-10 and IFN-γ. We suggest that Ad-IL-10/IL-12 infected DCs can prevent the rise of asthma effectively. In addition, this modified DCs applied to the established asthmtic animal model and the same therapeutic effect was observed.
In conclusion, we suggest that Ad-IL-10/IL-12 infected DCs induce a group of IL-10+ and IFN-γ+ T cells in vivo and such specific T cells can suppress the airway inflammation of asthmatic animal. Thus, such modified DCs may provide a more appropriate tool in future application of gene therapy for allergic diseases.

並列關鍵字

IL-10 ； IL-12 ； immune ； asthma

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