Inhibition of allergic inflammation in the lung by plasmid DNA allergen immunization
Autor: | Mark Roman, David H. Broide, Eyal Raz, Hans L. Spiegelberg, H Tighe |
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Rok vydání: | 1999 |
Předmět: |
Pulmonary and Respiratory Medicine
biology business.industry medicine.medical_treatment Immunotherapy respiratory system Eosinophil medicine.disease_cause Immunoglobulin E Molecular biology respiratory tract diseases Allergic inflammation Allergen Immune system medicine.anatomical_structure Antigen Pediatrics Perinatology and Child Health Immunology biology.protein Medicine business Antigen-presenting cell |
Zdroj: | Pediatric Pulmonology. 27:118-121 |
ISSN: | 1099-0496 8755-6863 |
Popis: | 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. |
Databáze: | OpenAIRE |
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