Induction of adaptive T regulatory cells that suppress the allergic response by coimmunization of DNA and protein vaccines.
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.
Jin
Huali
H
State Key Laboratory for Agro-Biotechnology, China Agricultural University, Beijing 100094, China.
Kang
Youmin
Y
Zhao
Lin
L
Xiao
Chong
C
Hu
Yanxin
Y
She
Ruiping
R
Yu
Yang
Y
Du
Xiaogang
X
Zhao
Gan
G
Ng
Terry
T
Chu
Hsien-Jue
HJ
Wang
Bin
B
D000485:Allergens / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D005423:Siphonaptera / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D017778:Vaccines, Combined / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D000485:Allergens; D017778:Vaccines, Combined; D019444:Vaccines, DNA