Inhibition of allergic inflammation in the lung by plasmid DNA allergen immunization.
The nature of the immune response (Th1/Th2) in mice to protein antigens or allergens was compared to that of immunization with pDNA encoding the same antigens. pDNA immunization induced a Th1 response and no IgE antibodies whereas the proteins induced a Th2 response and IgE antibodies. Furthermore, the pDNA induced Th1 response dominated over the protein elicited Th2 response in a secondary immune response. In particular, a preexisting Th2 response (as is the case in allergic patients) did not prevent a new Th1 response to an allergen-pDNA booster injection. The major reason why pDNA immunization induced a Th1 response to allergens was the presence of immunostimulatory non-coding DNA sequences (ISS) in the plasmid constructs having a CpG motif. These ISS caused antigen presenting cells to secrete INF-alpha, INF-beta and IL-12, all cytokines that induce naive T cells to differentiate into CD4+ Th1 cells and CD8+ Tc1 cells. Passive transfer of both Th1 and Tc1 cells from pDNA immunized mice into naive mice inhibited a Th2 response and IgE antibody formation to a subsequent injection of allergen in alum. pDNA immunization or ISS-oligonucleotide injection prior to allergen challenge reduced both immediate type airway sensitivity and late phase allergen induced eosinophil filtration of the lung. Allergen-pDNA immunization may provide a novel type of immunotherapy for the treatment of allergic diseases in man. Since only small amounts of allergen are secreted by the allergen-pDNA transformed cells, allergen-pDNA immunotherapy will unlikely carry the risk of the anaphylactic reactions that are associated with classical allergen injection immunotherapy.
Spiegelberg
H L
HL
Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla 92093-0833, USA. hansspiege@aol.com
Broide
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Tighe
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Roman
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D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000235:genetics*; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D004247:DNA / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007167:Immunotherapy / Q000379:methods; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D000941:Antigens; D004247:DNA