Oral tolerance induction to Dermatophagoides pteronyssinus and Blomia tropicalis in sensitized mice: occurrence of natural autoantibodies to immunoglobulin E.
BACKGROUND
The dust mites Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) are important sources of indoor allergens in tropical and subtropical countries. Murine models allow the analysis of the immune response and regulation of IgE production to Dp and Bt allergens. Oral tolerance induces unresponsiveness in naive animals, but its application in sensitized animals can provide useful information to improve allergy therapy.


OBJECTIVE
To study the profile of IgE and IgG subclasses antibody upon oral administration with Bt and Dp extract in previously sensitized mice. Further, the occurrence of autoantibodies IgG anti-IgE in the immunization and in the oral tolerance was investigated.


METHODS
A/Sn mice were immunized with Bt or Dp extract in alum, orally administrated with 0.25 mg of Bt or Dp extract or PBS at the 6th, 7th and 8th days after immunization and boosted twice with their respective allergens. To analyse the mice groups, specific IgE antibodies were measured by passive anaphylaxis reaction and specific IgG subclasses and anti-IgE IgG autoantibody by ELISA assay.


RESULTS
IgE levels were markedly increased in Bt-immunized mice compared with Dp-immunized mice. A distinct profile of the specific isotypes was verified in Bt-immunized mice with a preferential production of IgG3 and IgA antibodies, whereas Dp-immunized mice developed high titres of anti-Dp IgG1, IgG2a and IgG2b antibodies. The antigen feeding inhibited IgE response in both fed-mice groups but only Dp-fed mice presented decreased levels of IgG antibodies. Free anti-IgE IgG autoantibodies were detected mainly in the Dp-immunization and they correlated with the antibody isotypes found against the allergen.


CONCLUSIONS
This is the first time that the murine-type I hypersensitivity is employed to study Bt-immunization, showing a marked IgE production, associated with IgG response, which is at least in part driven by T-independent antigens. The oral tolerance protocol in previously sensitized animals was able to down-modulate IgE response and points out this route as a strategy for allergy therapy.
Sato
M N
MN
Laboratory of Allergy and Clinical and Experimental Immunology, School of Medicine of São Paulo, São Paulo, Brazil. marisato@usp.br
Oliveira
C R
CR
Futata
E A
EA
Victor
J R
JR
Maciel
M
M
Fusaro
A E
AE
Carvalho
A F
AF
Duarte
A J S
AJ
D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage*; D001323:Autoantibodies / Q000276:immunology*; D004391:Dust; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D051381:Rats
D000485:Allergens; D039741:Antigens, Dermatophagoides; D001323:Autoantibodies; D004391:Dust; D007074:Immunoglobulin G; D007073:Immunoglobulin E