Allergen-specific immunosuppression by ovalbumin fused with diphtheria toxin in mice sensitized with albumins of different origin.
BACKGROUND
We previously reported that ovalbumin-diphtheria toxin (OVA-DT) fusion protein eliminates mast cells bearing OVA-specific IgE and protects OVA-sensitized mice from fatal anaphylaxis induced by OVA challenge.


OBJECTIVE
To prove the specificity of therapeutic effect of OVA-DT to allergy induced by OVA only and not by other allergens such as human serum albumin (HSA), and to examine the cytotoxic effect of OVA-DT on B cells bearing OVA-specific IgE.


METHODS
Mice were sensitized with two different antigens, OVA and HSA, and then treated with OVA-DT. The therapeutic effect of OVA-DT on the allergy response to each of allergen was evaluated by anaphylactic test. The effect of OVA-DT on the production of allergen-specific Ig isotypes of the sensitized mice and the cytotoxic effect of OVA-DT on B cells expressing OVA-specific IgE were examined.


RESULTS
OVA-DT suppressed only OVA-induced allergy but not HSA-induced allergy in mice sensitized with a mixture of OVA and HSA. The suppression was prolonged even to the mice boosted with the same allergen 14 days after last treatment of OVA-DT. In addition, when the sensitized mice were boosted with the same allergens 14 days after last treatment of OVA-DT, the mice showed to increase the production of OVA-specific IgG2a/IgG3 and decreased that of OVA-specific IgE. OVA-DT targeted B cells bearing OVA-specific IgE, and killed them by DT-mediated cytotoxicity.


CONCLUSIONS
The therapeutic effect of OVA-DT was specific to OVA-induced allergy and the suppression of OVA-induced allergy was continuously shown in the mice boosted with the same allergens. This is considered to be caused by the increase of OVA-specific IgG2a and IgG3, and because of the decrease of OVA-specific IgE by killing of B cells bearing OVA-specific IgE.
Lee
B K
BK
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea. bkl4646@yumc.yonsei.ac.kr
Yoo
J E
JE
Jang
Y S
YS
Kim
J Y
JY
Hong
C S
CS
Ro
J Y
JY
D000418:Albumins / Q000276:immunology*; D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004167:Diphtheria Toxin / Q000276:immunology*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D012709:Serum Albumin / Q000276:immunology
D000418:Albumins; D000485:Allergens; D004167:Diphtheria Toxin; D007074:Immunoglobulin G; D012709:Serum Albumin; D007073:Immunoglobulin E; D010047:Ovalbumin