ORAL administration of antigen is used to induce antigen-specific peripheral immune tolerance1,2. As well as preventing systemic immune responses to ingested proteins3, oral tolerance to autoanti-gens has also been used to suppress autoimmune diseases in animals4-10and humans11,12. Both active suppression and clonal anergy are suggested to be mechanisms of oral tolerance, depending on the dose of antigen fed13,14. Here we report that oral antigen can delete antigen-reactive T cells in Peyer's patches, in mice transgenic for the ovalbumin-specific T-cell receptor genes. The deletion was mediated by apoptosis, and was dependent on dosage and frequency of feeding. At lower doses deletion was not observed; instead there was induction of antigen-specific cells that produced transforming growth factor (TGF)-β and interleukin (IL)-4 and IL-10 cytokines. At higher doses, both Thl and Th2 cells were deleted following their initial activation, whereas cells which secrete TGF-β were resistant to deletion. These findings demonstrate that orally administered antigen can induce tolerance not only by active suppression and clonal anergy but by extrathymic deletion of antigen-reactive Th1 and Th2 cells.
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Immune Modulation and Prevention of Autoimmune Disease by Repeated Sequences from Parasites Linked to Self Antigens
Journal of Neuroimmune Pharmacology (2016)