[Application of oral tolerance to the treatment of autoimmune diseases--active suppression and bystander suppression]

Oral tolerance is a phenomenon in which an orally ingested antigen induces systemic hyporesponsiveness to the same antigen. If the mechanism can be applied to autoantigens, it could be a promising mode of antigen-specific immunomodulatory treatment for patients with autoimmune diseases. Multiple ingestion of low doses of antigen induces active suppression. Under this condition, suppression of autoimmune attack to target tissues is mediated by anti-inflammatory cytokines such as TGF-beta, which are released from regulatory T cells triggered antigen-specifically. This type of oral tolerance, termed "bystander suppression", has one advantage of needing to know only the major components of the target tissue instead of exact epitopes of autoimmunity. Utilizing this mechanism, clinical trials of oral tolerance therapy are going on among the patients with multiple sclerosis, rheumatoid arthritis, and uveitis.