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 releva nce as a strategy to modulate allergy. In this study, the A/Sn mice sensiti zed with extract of Dermatophagoides pteronyssinus (Dp) and submitted to or al Dp administration showed a marked decrease in IgE anti-Dp antibody produ ction 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 Ig G1 antibody levels. The analysis of cytokine profile after Dp feeding showe d a significant decrease in interleukin-4 (IL-4), IL-5, and IL-13 antigen-i nduced secretion levels by spleen cells, without shifting to IL-2 and inter feron-gamma (IFN-gamma) production. Both transforming growth factor-beta (T GF-beta) baseline and TGF-beta antigen-stimulated levels were increased in Dp-fed mice. The effects of regulatory cytokines on anti-Dp IgE antibody pr oduction 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 an ti-TGF-beta, induced a marked inhibition of IgE production. Therefore, a ne gative modulatory effect on IgE response by inhibition of the axis Th2 was observed in sensitized Dp-fed mice, possibly mediated by induction of regul atory cytokines.