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

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4(+) T cells and IL-5, To determine whether the induction of oral tolerance down-regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of oral administration of a protein antigen on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on antigen-induced CD4(+) T cell infiltration and IL-5 production in the airways, and on the in vitro production of IL-2, IL-4, IL-5 and IFN-gamma in spleen cells of the mice. Oral administration of a protein antigen in high doses inhibited antigen-induced eosinophil infiltration in the trachea and IgE antibody production in mice in an antigen-specific manner. The oral administration of antigen also suppressed both CD4(+) T cell recruitment into the trachea and IL-5 levels in the bronchoalveolar lavage fluids of the mice 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 T(h)1 and T(h)2 cell tolerance in vivo. On the other hand, pretreatment with anti-transforming growth factor-beta antibody at the time of immunization with antigen had no significant effect on the inhibition of antigen-induced eosinophil recruitment and IgE antibody production in antigen-fed mice. Finally, antigen-specific CD4(+) T cells were not deleted in TCR transgenic mice after antigen feeding by FACS analysis. Taken together, these results indicate that high-dose oral tolerance induces not only T(h)1 but also T(h)2 cell tolerance in vivo and thereby inhibits antigen-induced eosinophil recruitment into the tissue.