INDUCTION OF RAPID T-CELL ACTIVATION AND TOLERANCE BY SYSTEMIC PRESENTATION OF AN ORALLY-ADMINISTERED ANTIGEN

To understand how orally introduced antigen regulates peripheral immun e responses, we fed cytochrome c protein to mice transgenic for the be ta chain of a cytochrome c-specific TCR and followed the antigen-speci fic T cell responses with a cyt c/I-E-k tetramer staining reagent. We find that within 6 hr of cytochrome c administration, antigen-specific systemic T cell activation is induced, and spleen cells gain the abil ity to stimulate cytochrome c-specific T cell responses. Feeding multi ple low doses of cytochrome c down-regulates the systemic immune respo nse, which can be correlated with a reduction of antigen-specific T ce lls and not with immune deviation. These results suggest that systemic distribution of antigen contributes significantly to oral tolerance i nduction.