Oral tolerance induction in dermatophagoides pteronyssinus-sensitized mice induces inhibition of IgE response and upregulation of TGF-beta secretion.
Oral antigen administration induces peripheral tolerance in naive animals. Studies of oral tolerance induction in sensitized mice have clinical relevance as a strategy to modulate allergy. In this study, the A/Sn mice sensitized with extract of Dermatophagoides pteronyssinus (Dp) and submitted to oral Dp administration showed a marked decrease in IgE anti-Dp antibody production compared with sensitized phosphate-buffered saline (PBS)-fed mice. T cells from Dp-fed mice cocultured with spleen cells from PBS-fed mice were able to inhibit IgE anti-Dp antibody production and did not interfere in IgG1 antibody levels. The analysis of cytokine profile after Dp feeding showed a significant decrease in interleukin-4 (IL-4), IL-5, and IL-13 antigen-induced secretion levels by spleen cells, without shifting to IL-2 and interferon-gamma (IFN-gamma) production. Both transforming growth factor-beta (TGF-beta) baseline and TGF-beta antigen-stimulated levels were increased in Dp-fed mice. The effects of regulatory cytokines on anti-Dp IgE antibody production were investigated in vitro. The addition of recombinant TGF-beta (rTGF-beta) to spleen cell cultures stimulated by Dp inhibited IgE antibody secretion in both mouse groups. Neutralizing antibodies to IL-4, but not anti-TGF-beta, induced a marked inhibition of IgE production. Therefore, a negative modulatory effect on IgE response by inhibition of the axis Th2 was observed in sensitized Dp-fed mice, possibly mediated by induction of regulatory cytokines.
Sato
M N
MN
Clinical and Experimental Allergy and Immunology Laboratory, LIM-56, School of Medicine, University of São Paulo, Brazil. marisato@usp.br
Fusaro
A E
AE
Victor
J R
JR
Oliveira
C R
CR
Futata
E T
ET
Maciel
M
M
Carvalho
A F
AF
Duarte
A J
AJ
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D039741:Antigens, Dermatophagoides; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008925:Mites / Q000276:immunology*; D010323:Passive Cutaneous Anaphylaxis; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D006023:Glycoproteins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007073:Immunoglobulin E