Oligodeoxynucleotides containing CpG motifs modulate the allergic TH2 response of BALB/c mice to Bet v 1, the major birch pollen allergen.
BACKGROUND
The use of adequate adjuvants to modulate the allergic T(H2)-type immune response is a promising concept for future immunotherapy of type I allergy. Bacterial DNA or oligodeoxynucleotides containing CpG motifs (CpG-ODNs) have been demonstrated to foster T(H1)-type immune responses.


OBJECTIVE
We investigated the adjuvanticity of CpG-ODNs and their capability to modulate the allergic T(H2) response in a mouse model.


METHODS
BALB/c mice were treated with CpG-ODNs and Bet v 1, the major birch pollen allergen, in different experimental setups. Allergen-specific antibody responses, T(H) cytokines, and eosinophilic infiltration of the airways were investigated.


RESULTS
Intraperitoneal administration of Bet v 1 together with aluminium hydroxide led to a typical T(H2) response. In contrast, coadminstration of CpG-ODNs with Bet v 1 in aluminium hydroxide resulted in markedly increased T(H1) activities (high IgG2a levels) and subsequently to reduced airway inflammation. The T(H1)-like immune response indicated by these humoral findings was also reflected by decreased IL-5 and increased IFN-gamma levels in cell cultures. CpG-ODNs as sole adjuvants with Bet v 1 did not lead to measureable Ig responses after subcutaneous or intraperitoneal immunizations; after intranasal application, 3 of 10 mice reacted. Nevertheless, a prophylactic effect was obtained with all routes tested; that is, mice treated subsequently with an established aerosol sensitization protocol displayed altered immune responses characterized by drastically elevated levels of Bet v 1-specific IgG2a, indicating a T(H1)/T(H0)-like immunity. Application of CpG-ODNs after aerosol sensitization also induced IgG2a.


CONCLUSIONS
By inducing T(H1)/T(H0)-biased immune responses to allergens, the use of CpG-ODNs as adjuvants may have important impacts for new forms of specific immunotherapy in type I hypersensitivity.
Jahn-Schmid
B
B
Institute of General and Experimental Pathology, Division of Immunopathology, University of Vienna, Vienna, Austria.
Wiedermann
U
U
Bohle
B
B
Repa
A
A
Kraft
D
D
Ebner
C
C
D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D052179:Antigens, Plant; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014197:Trees
D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; D009838:Oligodeoxyribonucleotides; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula