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) 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.
Broide
D H
DH
Department of Medicine, University of California, San Diego, La Jolla 92093, USA. dbroide@ucsd.edu
Stachnick
G
G
Castaneda
D
D
Nayar
J
J
Miller
M
M
Cho
J Y
JY
Roman
M
M
Zubeldia
J
J
Hayashi
T
T
Raz
E
E
Hyashi
T
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D001483:Base Sequence; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007073:Immunoglobulin E; D010047:Ovalbumin; D004247:DNA