Inhibition of immunoglobulin E response to Japanese cedar pollen allergen (Cry j 1) in mice by DNA immunization: different outcomes dependent on the plasmid DNA inoculation method.
To develop a new immunotherapy for Japanese cedar (Cryptomeria japonica; CJ) pollinosis, we evaluated the use of DNA immunization by inoculating mice with plasmid DNA encoding Cry j 1 as a CJ pollen major allergen (pCACJ1). Repeated intramuscular (i.m.) inoculation of BALB/c mice with pCACJ1 produced anti-Cry j 1 antibody responses, which were predominately of the immunoglobulin G2a (IgG2a) type. Furthermore, this inoculation suppressed immunoglobulin E (IgE) and IgG1 antibody responses to subsequent alum-precipitated Cry j 1 injections. Splenic T cells isolated from mice inoculated with pCACJ1 i.m. secreted interferon-gamma (IFN-gamma), but not interleukin (IL)-4, in vitro upon stimulation with Cry j 1 as well as with p277-288, a peptide corresponding to the T-cell epitope of Cry j 1. In contrast, inoculation of BALB/c mice with pCACJ1 by gene gun injection caused response predominantly of the IgG1 type, and enhanced production of anti-Cry j 1 IgE antibodies to subsequent alum-precipitated Cry j 1 injections. Splenic T cells isolated from pCACJ1-innoculated mice by gene gun injection secreted both IFN-gamma and IL-4 in vitro, upon stimulation with Cry j 1 as well as with p277-288. These findings suggest that i.m. inoculation with pCACJ1 effectively elicits Cry j 1-specific T helper 1 (Th1)-type immune responses, resulting in inhibition of the IgE response to Cry j 1.
Toda
M
M
Department of Immunology, AIDS Research Center and Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.
Sato
H
H
Takebe
Y
Y
Taniguchi
Y
Y
Saito
S
S
Inouye
S
S
Takemori
T
T
Sakaguchi
M
M
D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D019470:Biolistics; D018929:Cell Culture Techniques; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D007108:Immune Tolerance; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000627:therapeutic use
D000485:Allergens; D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; D010940:Plant Proteins; D019444:Vaccines, DNA; D007073:Immunoglobulin E