Vaccinations with T-helper type 1 directing adjuvants have different suppressive effects on the development of allergen-induced T-helper type 2 responses
| Autor: | K. D. Mayer, Susanne M. Grunewald, Tobias Polte, G. Hansen, Claudia M. Trujillo-Vargas, Klaus J. Erb, Gisela Wohlleben, Thomas Bickert, José R. Ramírez-Pineda, Alois Palmetshofer |
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| Rok vydání: | 2005 |
| Předmět: |
Allergy
Neutrophils Ovalbumin medicine.medical_treatment Respiratory System Immunology Tuberculin Immunoglobulin E complex mixtures Interferon-gamma Mice chemistry.chemical_compound Th2 Cells Immune system Adjuvants Immunologic Immune Tolerance medicine Animals Immunology and Allergy Eosinophilia Cells Cultured biology business.industry Alum Macrophages Vaccination Allergens Th1 Cells respiratory system medicine.disease Adoptive Transfer Interleukin-12 respiratory tract diseases Eosinophils Mice Inbred C57BL Oligodeoxyribonucleotides chemistry BCG Vaccine biology.protein Female Nasal administration medicine.symptom business Adjuvant |
| Zdroj: | Clinical Experimental Allergy. 35:1003-1013 |
| ISSN: | 1365-2222 0954-7894 |
| DOI: | 10.1111/j.1365-2222.2005.02287.x |
| Popis: | Summary Background Allergen-induced T-helper type 2 (Th2) responses can be inhibited with Th1 directing vaccines. However, studies comparing the efficacy of the different adjuvants have not been performed in detail. Objective For this reason we compare the effects of live Bacillus–Calmette–Guerin(BCG), heat-killed (hk)-BCG, CpG-ODN (oligodeoxynucleotide) or PPD on the development of allergen-induced Th2 responses in mice. Methods Ovalbumin (OVA)-specific allergic responses were induced in C57BL/6 mice by two intraperitoneally (i.p.) applications of OVA/alum followed by the intranasal challenge with OVA. The different Th1-inducing adjuvants were applied to the mice together with OVA/alum i.p. during the OVA-sensitization period and, subsequently, different parameters of allergic immune responses were evaluated. Results All the adjuvants were effective in inhibiting the development of allergen-induced airway eosinophilia, mucous production and, with the exception of PPD, also airway hyper-reactivity, when they were applied together with OVA/alum. However, allergen-specific IgG1 and IgE serum levels were only reduced in live BCG- and PPD-treated mice. Suppression of airway eosinophilia was not observed in IFN-γ- or IL-12-deficient mice (hk-BCG, CpG-ODN and PPD). Interestingly, live BCG was still able to suppress allergen-induced Th2 responses in the absence of either IFN-γ or IL-12. When mice vaccinated with the different adjuvants together with OVA/alum were subjected to a second period of OVA/alum immunization, only live and hk-BCG were able to efficiently suppress the development of airway inflammation. This effect could be adoptively transferred by splenic CD4+ T cells. Conclusions Taken together our data suggest that live BCG>hk-BCG>CpG-ODN >PPD are effective in suppressing allergen-induced Th2 responses. The degree of suppression and the component of the Th2 response affected (airway inflammation vs. the production of allergen-specific IgE and IgG1) were dependent upon the adjuvant used and how it was applied. Our results contribute to the design of novel vaccines protecting humans from developing allergic disorders. |
| Databáze: | OpenAIRE |
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