Induction of adaptive T regulatory cells that suppress the allergic response by coimmunization of DNA and protein vaccines.

نویسندگان

  • Huali Jin
  • Youmin Kang
  • Lin Zhao
  • Chong Xiao
  • Yanxin Hu
  • Ruiping She
  • Yang Yu
  • Xiaogang Du
  • Gan Zhao
  • Terry Ng
  • Hsien-Jue Chu
  • Bin Wang
چکیده

Allergen-induced immediate hypersensitivity (AIH) is a health issue of significant concern. This robust inflammatory reaction is initiated by the allergen-specific T cell responsiveness. Severe lesion reactions on skin are consequential problem requiring medical treatment. Effective Ag-specific treatments or preventions are lacking. Using a rodent model of AIH induced by flea allergens, we first report that coimmunization of DNA and protein vaccines encoding the flea salivary specific Ag-1 ameliorated experimental AIH, including Ag-induced wheal formation, elevated T cell proliferation, and infiltration of lymphocytes and mast cells to the site of allergen challenge. The amelioration of AIH was directly related to the induction of a specific population of flea antigenic specific T cells exhibiting a CD4(+)CD25(-)FoxP3(+) phenotype, a characteristic of regulatory T (T(REG)) cells. These T(REG) cells expressing IL-10, IFN-gamma, and the transcriptional factor T-bet after Ag stimulation were driven by a tolerogenic MHC class II(+)/CD40(low) dendritic cell population that was induced by the coimmunization of DNA and protein vaccines. The tolerogenic dendritic cell could educate the naive T cells into CD4(+)CD25(-)FoxP3(+) T(REG) cells both in vitro and in vivo. The study identified phenomenon to induce an Ag-specific tolerance via a defined Ag vaccinations and lead to the control of AIH. Exploitation of these cellular regulators and understanding their induction provides a basis for the possible development of novel therapies against allergic and related disorders in humans and animals.

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Coimmunization of DNA and Protein That Suppress the Allergic Response by Induction of Adaptive T Regulatory Cells

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عنوان ژورنال:
  • Journal of immunology

دوره 180 8  شماره 

صفحات  -

تاریخ انتشار 2008