High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the mouse airways

We have previously shown that antigen-induced eosinophil recruitment intothe tissue of sensitized mice is mediated by CD4+ T cells and IL- 5. Todetermine whether the induction of oral tolerance down-regulatesantigen-induced eosinophil recruitment into the tissue, we studied theeffect of oral administration of a protein antigen on antigen-inducedeosinophil infiltration in the trachea of sensitized mice, on antigen-induced CD4+ T cell infiltration and IL-5 production in the airways, and onthe in vitro production of IL-2, IL-4, IL-5 and IFN-gamma in spleen cellsof the mice. Oral administration of a protein antigen in high dosesinhibited antigen-induced eosinophil infiltration in the trachea and IgEantibody production in mice in an antigen-specific manner. The oraladministration of antigen also suppressed both CD4+ T cell recruitment intothe trachea and IL-5 levels in the bronchoalveolar lavage fluids of themice after antigen inhalation. In vitro antigen-induced production of IL-2,IFN-gamma, IL-4 and IL-5 was decreased in spleen cells of antigen-fed mice,indicating the induction of both Th1 and Th2 cell tolerance in vivo. On theother hand, pretreatment with anti-transforming growth factor-beta antibodyat the time of immunization with antigen had no significant effect on theinhibition of antigen-induced eosinophil recruitment and IgE antibodyproduction in antigen-fed mice. Finally, antigen-specific CD4+ T cells werenot deleted in TCR transgenic mice after antigen feeding by FACS analysis.Taken together, these results indicate that high-dose oral toleranceinduces not only Th1 but also Th2 cell tolerance in vivo and therebyinhibits antigen-induced eosinophil recruitment into the tissue.