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

Hidekazu Shirota, Kunio Sano, Tadashi Kikuchi, Gen Tamura, Kunio Shirato

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5575-5582
Number of pages8
JournalJournal of Immunology
Volume164
Issue number11
DOIs
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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