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 activity of Th2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype. We have previously reported that intratracheal coadministration of CpG and allergen inhibited airway eosinophilia and hyperresponsiveness in a synergistic manner. To substantiate the synergism between CpG and Ag, we introduced a covalently linked conjugate between CpG and Ag and examined 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 inhibitory effects lasted for at least 2 mo. The inhibition of airway eosinophilia by the conjugate was Ag specific and associated with an improvement of the airway hyperresponsiveness and the unresponsiveness of the Ag-specific Th2 cells in the regional lymph nodes. The CpG-Ag conjugate was 100-fold more effective than the unconjugated mixture for inducing in vitro Th1 differentiation 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 inhalation of allergen-CpG conjugate could be a desensitization therapy for patients with bronchial asthma.
Shirota
H
H
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sano
K
K
Kikuchi
T
T
Tamura
G
G
Shirato
K
K
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000473:pathology; D004338:Drug Combinations; D004802:Eosinophilia / Q000276:immunology* / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D007108:Immune Tolerance; D007442:Intubation, Intratracheal; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D004338:Drug Combinations; D018984:Epitopes, T-Lymphocyte; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D010047:Ovalbumin