Inhibition of specific IgE response in vivo by allergen-gene transfer.
DNA immunization has been an attractive approach in altering the host immune response to antigen. To examine the utility of DNA immunization in allergic response, we examined the in vivo efficacy of an 'allergen-gene immunization' approach in the modulation of allergen-specific IgE responses in mice. Our results showed first that I.m. injection of a gene construct (pCMVD) containing an important house dust mite allergen gene (Dermatophagoides pteronyssinus group 5 allergen; Der p 5) results in the induction of Der p 5-specific IgG antibodies, but not IgE antibody. We next examined the effect of transduced allergen gene on the expression of specific IgE response in mice after i.p. challenge with recombinant Der p 5 (rDer p 5). Both vector (mock) control- and pCMVD-treated mice were i.p. sensitized with rDer p 5 at 3 weeks after injection of gene construct. Results showed that there is a 90% reduction in the level of specific IgE in pCMVD-treated mice when compared with mock-treated mice. Furthermore, the suppression of specific IgE response can be adoptively transferred with CD8+ T cells from pCMVD-treated mice and such inhibition is in an antigen-specific manner, since the level of specific IgE to an irrelevant allergen, Der p 1, remained unchanged in comparison to that of the mock-treated group. In addition, Der p 5-specific CD8+ T cells could produce high levels of IFN-gamma which probably inhibit allergen-specific IgE responses. Taken together, our results suggest that allergen-gene transfer is effective in the modulation of allergen-specific IgE responses and may provide a novel therapeutic approach.
Hsu
C H
CH
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipai, ROC.
Chua
K Y
KY
Tao
M H
MH
Huang
S K
SK
Hsieh
K H
KH
D019264:Adoptive Transfer; D000485:Allergens / Q000235:genetics* / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis; D004274:DNA, Recombinant / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D007114:Immunization / Q000379:methods*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D008925:Mites / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*
D000485:Allergens; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D004274:DNA, Recombinant; D006023:Glycoproteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E