PERIPHERAL DELETION OF ANTIGEN-REACTIVE T-CELLS IN ORAL TOLERANCE

ORAL administration of antigen is used to induce antigen-specific peri pheral immune tolerance(1,2). As well as preventing systemic immune re sponses to ingested proteins(3), oral tolerance to autoantigens has al so been used to suppress autoimmune diseases in animals(4-10) and huma ns(11,12). Both active suppression and clonal anergy are suggested to be mechanisms of oral tolerance, depending on the dose of antigen fed( 13,14). Here we report that oral antigen can delete antigen-reactive T cells in Peyer's patches, in mice transgenic for the ovalbumin-specif ic T-cell receptor genes, The deletion was mediated by apoptosis, and was dependent on dosage and frequency of feeding. At lower doses delet ion was not observed; instead there was induction of antigen-specific cells that produced transforming growth factor (TGF)beta and interleuk in (IL)-4 and IL-10 cytokines. At higher doses, both Th1 and Th2 cells were deleted following their initial activation, whereas cells which secrete TGF-beta were resistant to deletion. These findings demonstrat e that orally administered antigen can induce tolerance not only by ac tive suppression and clonal anergy