Application of bone marrow-derived dendritic cells to modulate immune response in animal model of allergen sensitization

• Main Authors: Hsu Nai-Yun, 許乃云
• Other Authors: 江伯倫
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/54093447225708232297

碩士 === 國立臺灣大學 === 免疫學研究所 === 89 === Allergic asthma is a serious atopic disease worldwide, both in the developing and developed countries. In the patients of allergic asthma, it is well characterized by skewed polarization of helper T cell development toward type 2 T helper cell with increased production of interleukin 4(IL-4) and IL-5 which could result in IgE production, airway inflammation and airway hyperresponsiveness(AHR). Several reports suggested antigen such as ovalbumin could be used to estabilish an animal model of asthma for future investigation of mechanism and therapy application . Dendritic cells(DCs), a professional antigen presenting cells, play a critical role not only in the T cell priming but also the type of T cell mediated response. It is proposed that different dendritic cell subsets and their activation/maturation stage may generate distinct immune response. The aim of our study is to modulate immune response in an OVA-induced asthma model and further prevent airway inflammation、AHR, and IgE production after OVA sensitization by using bone marrow derived dendritic cells. In the study, bone marrow cells cultured with granulocyte macrophage colony stimulating factor and IL-4 could generate dendritic cells with the characteristic expression of B7.1、B7.2、33D1 , high level IAd molecules and their mophology. In addition, OVA pulsed dendtitic cells were used to induce an antigen-specific immune response. Serum OVA specific IgE level of OVA pulsed dendritic cells pretreated mice is higher than Hank’s balanced salt solution(HBSS) pretreated mice after 21 days of 1st OVA injection. However there is no significant difference in the percentage of eosinophil in bronchoalveolar lavage fluid and AHR between OVA-pulsed dendritic cells pretreated mice and HBSS pretreated mice after OVA sensitization. The result is opposite to our expectation. We speculated that the Th1 dominated immune response failed to be induced maybe the major reason. So we decided to culture DCs with LPS or infected with recombinant adenovirus which could express IL-12 in mammalian cells. Increased secretion of IL-12 could be observed after these treatments. In conclusion ,OVA -pulsed DCs fail to diminish AHR、airway inflammation、and IgE production，lipopolysaccharide modified and adenoviral engineering DCs may be promising candidates。