Mite Allergen Immunotherapy Influences on Dendritic Cell Function in Allergic Asthmatic Children

• Main Author: 王壯銘
• Other Authors: 莊晶晶
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/35394662750366014268

碩士 === 國立嘉義大學 === 微生物免疫與生物藥學系研究所 === 99 === Introduction：The prevalence of asthma is increasing among children in most industrialized countries. Allergic asthma is a Th2 inflammatory disease. Dendritic cells (DCs) can stimulate naïve T cells and play a role in their instruction to become Th1 or Th2 cells. DCs can express a variety of surface markers on their surface, and it has been proposed that the differential expression of these surface molecules by DCs influences Th1/Th2 switching. CD80 and CD86 may play important roles at different stages of T-cell activation. Furthermore, expression of CD40 and OX40 ligand on DCs may also favor Th2 differentiation. IL-12 is a critical Th1- polarizing cytokine, and absence of IL-12 facilitates the development of Th2 responses. Allergen-specific immunotherapy (allergen-SIT) represents the only curative treatment and has the potential to modify the course of allergy. SIT can switch the imbalance between Th1 and Th2 cytokine expression, and induce functional regulatory T cells. Therefore, to investigate the phenotypic and functional variation of DCs in children with allergic asthma that obtained SIT treatment, might understand the grounds of SIT influence in such diseases. The aim of this study was to identify the expression of important immune molecules (CD80, CD86, CD83, CD40, TLR4, HLA-DR and OX40L) expression on monocyte-derived dendritic cells (MoDCs) following mite allergen immunotherapy in allergic asthmatic children. In addition, we assessed the amounts of cytokines (IL-12 and IL-10) production from MoDCs after mite allergy immunotherapy. Methods： Peripheral blood monocytes from child patients with SIT-allergic asthma (SIT-AA), allergic asthma controls (control-AA) and healthy controls (HC) were cultured with GM-CSF and IL-4 for 5 days, respectively and subsequently stimulated with Dermatophagoides pteronyssinus (D.pt) or lipopolysaccharide (LPS) for another 24 hours to create mature monocyte-derived DCs (MoDCs). The expressions of CD86, CD80, CD83, CD40, HLA-DR and OX40L on MoDCs were assessed by fluorescence-activated cell sorter. IL-12 and IL-10 production by MoDCs was determined by ELISA. The relatively data in different groups would be also compared. Results： After complete SIT, LPS stimulated MoDCs from child patients, the expression of CD86 was similar to HC individuals. Nevertheless, control-AA individuals presented a relative higher degree. Additionally, compared with control-AA, SIT-AA individuals and HC persons tended to increase the surface expression of HLA-DR after LPS stimulation. TLR4 expression on D.pt-pulsed DCs of SIT-AA and HC persons showed higher degree as compared to those of control-AA persons. Production of IL-12 and IL-10 by MoDCs was similar among SIT-AA , control-AA and HC groups. Conclusion: SIT was associated with down-regulated expression of CD86 and increased expression of HLA-DR on MoDCs, which suggested that SIT might correct these intrinsic defects in MoDCs from allergic asthmatic children. SIT increased expression of TLR4 on MoDCs, therefore TLR4 agonists may be administered with allergen to amplify SIT effects.