2003 Fiscal Year Final Research Report Summary

Inhibition of pulmonary eosinophilia by Mucosal plasmid DNA immunization

Research Project

Project/Area Number	14570423
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	内科学一般
Research Institution	Dept. of Internal Medicine II, Fukushima Medical University School of Medicine
Principal Investigator	SATO Yukio Fukushima Medical University School of Medicine, Associate Professor of Medicine, 医学部, 教授 (20254013)
Co-Investigator(Kenkyū-buntansha)	KOBAYASHI Hiroko Fukushima Medical University School of Medicine, Associate Professor of Medicine, 医学部, 助手 (00336463) OHIRA Hiromasa Fukushima Medical University School of Medicine, Associate Professor of Medicine, 医学部, 講師 (90274951)
Project Period (FY)	2002 – 2003
Keywords	DNA VACCINE / ALLERGY / EOSINOPHILIA / MUCOSAL IMMUNITY / 粘膜
Research Abstract	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.