SUPPRESSION OF BRONCHIAL ASTHMA BY A DNA VACCINE ENCODING ALLERGEN

将编码抗原（Ag）的质粒DNA（pDNA）注射到胃壁，引起粘膜上皮细胞的转染，并诱导粪便伊加反应和全身抗体。相比之下，皮内递送pDNA诱导全身性抗体而不是粘膜伊加应答。经胃粘膜pDNA免疫的小鼠脾CD 4 +T细胞和纵隔淋巴结（MLN）细胞在体外Ag刺激后产生Th 1型细胞因子IFN-γ，但不产生IL-4或IL-5。来自用pDNA皮内免疫的小鼠的抗原刺激的脾CD 4 + T细胞产生IFN-γ，但来自这些小鼠的MLN细胞不产生IFN-γ。因此，由胃粘膜递送编码变应原的pDNA诱导的Th 1细胞可在吸入相应变应原后在肺中积累，并可产生IFN-γ，其随后直接防止吸入各种变应原后嗜酸性粒细胞的积累。我已经使用气道嗜酸性粒细胞增多的鼠模型证明，经胃粘膜用pDNA免疫的小鼠在气道激发后不仅用pDNA编码的相应Ag，而且用与相应Ag混合的不相关Ag保护免于气道嗜酸性粒细胞增多。相比之下，i.d. pDNA相同的人气道嗜酸性粒细胞增多症仅受相应抗原的保护，而不受与相应抗原混合的无关抗原的保护。因此，粘膜DNA免疫在预防气道嗜酸性粒细胞增多症方面可能比全身DNA免疫上级，因为粘膜递送编码单一变应原的pDNA可以防止由多种变应原诱导的嗜酸性粒细胞浸润。

Injection of plasmid DNA(pDNA) encoding antigen (Ag) to gastric wall caused transfection of mucosal epithelial cells and induced fecal IgA responses as well as systemic antibody. In contrast, intradermal delivery of pDNA induced systemic antibody but not mucosal IgA responses. Splenic CD4+T cells and mediastinal lymph node (MLN) cells of mice immunized via gastric mucosa with pDNA produce Th1-type cytokine, IFN-gamma, but not IL-4 or IL-5, after in vitro Ag-stimulation. The antigen-stimulated splenic CD4+ T cells from mice intradermally immunized with pDNA produced IFN-gamma, but MLN cells from these mice did not. Therefore, Th1 cells induced by gastric mucosal delivery of pDNA encoding allergen may accumulate at the lung after the inhalation of the corresponding allergen and may produce IFN-gamma that then prevent directly the accumulation of eosinophils following inhalation of various allergens. I have demonstrated using murine model of airway eosinophilia that mice immunized via gastric mucosa with pDNA were protected from airway eosinophilia following airway challenge not only with the corresponding Ag that the pDNA encodes, but also with the irrelevant Ag mixed with the corresponding Ag. In contrast mice immunized i.d. with same pDNA were protected from airway eosinophilia induced only by the corresponding Ag, but not by the irrelevant Ag mixed with the corresponding Ag. Therefore mucosal DNA immunization may be superior than systemic DNAimmunization in preventing airway eosinophilia in that mucosal delivery of pDNA encoding single allergen can protect against eosinophilic infiltration induced by multiple allergens.