Regulation of murine airway eosinophilia and Th2 cells by antigen-conjugated CpG oligodeoxynucleotides as a novel antigen-specific immunomodulator

The characteristic features of bronchial asthma reflect the orchestrated ac tivity of Th2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-d ominant phenotype. We have previously reported that intratracheal coadminis tration of CpG and allergen inhibited airway eosinophilia and hyperresponsi veness in a synergistic manner. To substantiate the synergism between CpG a nd Ag, we introduced a covalently linked conjugate between CpG and Ag and e xamined the efficacy on airway eosinophilia and Th2 cytokine production. We found that the conjugated form of CpG plus Ag was 100-fold more efficient in regulating airway eosinophilia than the unconjugated mixture. The inhibi tory effects lasted for at least 2 mo, The inhibition of airway eosinophili a by the conjugate was Ag specific and associated with an improvement of th e airway hyperresponsiveness and the unresponsiveness of the Ag-specific Th 2 cells in the regional lymph nodes. The CpG-Ag conjugate was 100-fold more effective than the unconjugated mixture for inducing in vitro Th1 differen tiation in an IL-12-dependent manner. Our data show that CpG conjugated to Ag can work as a novel Ag-specific immunomodulator and imply that inhalatio n of allergen-CpG conjugate could be a desensitization therapy for patients with bronchial asthma.