Adel-Patient Karine, Pothelune Laetitia, Ah-Leung Sandrine, Wal Jean-Michel, Créminon Christophe, Chatel Jean-Marc
Laboratoire INRA d'Immuno-Allergie Alimentaire, iBiTec-S/SPI Bât. 136-CEA de Saclay, 91191 Gif sur Yvette Cedex, France.
Clin Vaccine Immunol. 2010 Jan;17(1):36-42. doi: 10.1128/CVI.00275-09. Epub 2009 Nov 18.
Block copolymers were recently used to promote gene delivery in various tissues. Using a plasmid encoding a food allergen, bovine beta-lactoglobulin (BLG), we studied the effects of block copolymers on gene expression levels and primary immune response and on further induced allergy. Block copolymers (i.e., Tetronic 304, 908, and 1107) and various quantities of DNA were injected into the tibialis muscles of BALB/c mice. The BLG levels in injected muscle and the BLG-specific induced immune response were analyzed after injection. DNA-immunized mice were further experimentally sensitized with BLG, and the effects of block copolymer and DNA doses on allergic sensitization and elicitation were compared. Tetronic 304 induced a 12-fold increase in BLG production, while Tetronic 1107 increased the duration of BLG expression. Different Th1 primary specific immune responses were observed, either strong humoral and cellular (304), only cellular (1107), or weak cellular and humoral (908) responses. After BLG sensitization, increased BLG-specific IgG2a production was observed in all groups of mice independently of the presence and nature of the block copolymer. Increased BLG-specific IgG1 production was also detected after sensitization, except with Tetronic 1107. Compared with naked DNA, Tetronic 304 was the only block polymer that decreased BLG-specific IgE concentrations. However, after allergen challenge, Tetronic 1107 was the only block copolymer to reduce eosinophils and Th2 cytokines in bronchoalveolar lavage (BAL) fluid. Tetronic 304 amplified local inflammation. Each block copolymer elicited a different immune response, although always Th1 specific, in BALB/c mice.
嵌段共聚物最近被用于促进基因在各种组织中的传递。我们使用编码食物过敏原牛β-乳球蛋白(BLG)的质粒,研究了嵌段共聚物对基因表达水平、初次免疫反应以及进一步诱导过敏的影响。将嵌段共聚物(即Tetronic 304、908和1107)与不同量的DNA注射到BALB/c小鼠的胫肌中。注射后分析注射肌肉中的BLG水平以及BLG特异性诱导的免疫反应。对DNA免疫的小鼠用BLG进行进一步的实验性致敏,并比较嵌段共聚物和DNA剂量对过敏致敏和激发的影响。Tetronic 304使BLG产量增加了12倍,而Tetronic 1107延长了BLG的表达持续时间。观察到不同的Th1初次特异性免疫反应,即强烈的体液和细胞反应(304)、仅细胞反应(1107)或微弱的细胞和体液反应(908)。在BLG致敏后,所有小鼠组中均观察到BLG特异性IgG2a产生增加,与嵌段共聚物的存在和性质无关。致敏后还检测到BLG特异性IgG1产生增加,但Tetronic 1107组除外。与裸DNA相比,Tetronic 304是唯一能降低BLG特异性IgE浓度的嵌段聚合物。然而,在过敏原激发后,Tetronic 1107是唯一能减少支气管肺泡灌洗(BAL)液中嗜酸性粒细胞和Th2细胞因子的嵌段共聚物。Tetronic 304加剧了局部炎症。尽管在BALB/c小鼠中每种嵌段共聚物引发的免疫反应始终是Th1特异性的,但各有不同。