Inhibition of pulmonary eosinophilia by Mucosal plasmid DNA immunization

通过粘膜途径而非全身途径用质粒DNA免疫已显示在局部和远处粘膜部位产生辅助性T细胞-1（Th 1）偏向的全身性以及粘膜免疫。已经显示，通过全身途径用编码变应原的质粒DNA免疫接种可防止在注射氢氧化铝中的变应原蛋白后变应原特异性Th 2细胞的活化，并抑制特异性IgE合成。我们试图确定是否Th 1偏向粘膜质粒DNA免疫诱导的粘膜免疫抑制肺嗜酸性粒细胞增多症在卵清蛋白（OVA）致敏小鼠吸入后。结果表明，用编码OVA的质粒DNA（pCMV-OVA）经粘膜途径免疫Balb/c小鼠，而不是经皮内途径免疫。d.）途径，增强OVA吸入后支气管肺泡（BAL）液中的干扰素-γ（IFN-γ）水平。在OVA致敏之前通过粘膜途径用pCMV-OVA免疫抑制血清IgE应答和肺嗜酸性粒细胞增多。质粒DNA免疫能够在支气管粘膜中诱导Th 1偏向的粘膜免疫，并且即使在存在持续的Th 2应答的情况下也能够抑制气道嗜酸性粒细胞增多。因此，粘膜途径质粒DNA免疫可能比全身途径更有效地抑制肺变态反应。

Immunization with plasmid DNA through mucosal routes, but not systemic routes, has been shown to generate T-helper-1 (Th1)-biased systemic as well as mucosal immunity at local and distant mucosal sites. Immunization with plasmid DNA encoding an allergen via the systemic routes has been shown to prevent activation of allergen-specific Th2 cells following injection of allergen protein in aluminum hydroxide, and to inhibit specific lgE synthesis. We attempted to determine whether Th1-biased mucosal immunity induced by mucosal plasmid DNA immunization inhibits pulmonary eosinophilia in ovalbumin (OVA)-sensitized mice after OVA inhalation. The results showed that immunization of Balb/c mice with plasmid DNA encoding OVA, pCMV-OVA, via mucosal route, but not via an intradermal (i. d.) route, enhanced interferon-γ (IFN-γ) levels in bronchoalveolar (BAL) fluid after OVA inhalation. Immunization with pCMV-OVA via mucosal routes prior to OVA sensitization inhibited serum lgE responses and pulmonary eosinophilia These results suggested that i.g. plasmid DNA immunization is capable of inducing Th1-biased mucosal immunity in bronchial mucosa and of inhibiting airway eosinophilia even in the presence of an ongoing Th2 response. Therefore, plasmid DNA immnunization via mucosal routes may be more effective than that via systemic routes in inhibiting pulmonary allergic responses.