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