HIGH-DOSE ORAL TOLERANCE PREVENTS ANTIGEN-INDUCED EOSINOPHIL RECRUITMENT INTO THE MOUSE AIRWAYS

We have previously shown that antigen-induced eosinophil recruitment i nto the tissue of sensitized mice is mediated by CD4(+) T cells and IL -5, To determine whether the induction of oral tolerance down-regulate s antigen-induced eosinophil recruitment into the tissue, we studied t he effect of oral administration of a protein antigen on antigen-induc ed eosinophil infiltration in the trachea of sensitized mice, on antig en-induced CD4(+) T cell infiltration and IL-5 production in the airwa ys, and on the in vitro production of IL-2, IL-4, IL-5 and IFN-gamma i n spleen cells of the mice. Oral administration of a protein antigen i n high doses inhibited antigen-induced eosinophil infiltration in the trachea and IgE antibody production in mice in an antigen-specific man ner. The oral administration of antigen also suppressed both CD4(+) T cell recruitment into the trachea and IL-5 levels in the bronchoalveol ar lavage fluids of the mice after antigen inhalation. In vitro antige n-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 immu nization with antigen had no significant effect on the inhibition of a ntigen-induced eosinophil recruitment and IgE antibody production in a ntigen-fed mice. Finally, antigen-specific CD4(+) T cells were not del eted in TCR transgenic mice after antigen feeding by FACS analysis. Ta ken together, these results indicate that high-dose oral tolerance ind uces not only T(h)1 but also T(h)2 cell tolerance in vivo and thereby inhibits antigen-induced eosinophil recruitment into the tissue.