Systemic administration of immunostimulatory DNA sequences mediates reversible inhibition of Th2 responses in a mouse model of asthma

This study investigated whether immunostimulatory DNA sequences (ISS) induc e a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response t o ovalbumin (ova) and then administered a dose of ISS prior to ova inhalati on challenge. Mice were then rechallenged with ova by inhalation a second t ime at varying time points after the first ova inhalation (1 to 8 weeks lat er) to determine whether the ISS dose administered prior to the first ova i nhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of o va antigen, as well as 4 weeks later to the second inhalation of ova. Howev er, ISS did not inhibit a Th2 response to the second inhalation of ova 8 we eks later. The reversible inhibition of Th2 responses at 8 weeks suggests t he need for repeated ISS administration at monthly intervals.