Regulation of T-helper type 2 cell and airway eosinophilia by transmucosalcoadministration of antigen and oligodeoxynucleotides containing CpG motifs

The characteristic features of bronchial asthma. including airway eosinophi lia and elevated immunoglobulin (IE)E levels, are known to be orchestrated by T-helper (Th) 2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype, However, CpG may incur nonspecific Th1 activation a nd toxic effects, In this study we report a novel inhibition of Th2 cells b y transmucosal inoculation of antigen and CpG, Intratracheal instillation o f CpG inhibited airway eosinophilia and Th2 cytokine production in antigen- sensitized mice, The inhibition was observed when CpG was given at the same time or in advance of antigen challenge. Notably, concomitant administrati on of CpG and antigen las opposed to either one alone) was essential for th e inhibitory effects, The antigen dose could be minimized to avoid a harmfu l boost of eosinophilia, CpG had few effects on systemic anti-ovalbumin IEE responses, These results demonstrate that a synergism between transmucosal ly administered allergen and CpG inhibits Th2 cells in parallel with an imp rovement in airway eosinophilia and hyperresponsiveness without impeding sy stemic immune responses. Our data imply that inhalation of a minimal amount of allergen plus CpG could be a novel desensitization therapy for patients with bronchial asthma.