Systemic Administration of Immunostimulatory DNA Sequences Mediates Reversible Inhibition of Th2 Responses in a Mouse Model of Asthma |
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Authors: | David H Broide Greg Stachnick Diego Castaneda Jyothi Nayar Marina Miller Jae Youn Cho Mark Roman Jose Zubeldia Tomoko Hyashi Eyal Raz |
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Institution: | (1) Department of Medicine, University of California, San Diego, La Jolla, California, 92093 |
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Abstract: | This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals. |
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Keywords: | IL-5 eosinophils interferon- " target="_blank">gif" alt="gamma" align="MIDDLE" BORDER="0"> asthma CpG motif |
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