Oral tolerance: Elucidation of mechanisms and application to treatment of autoimmune diseases

Oral tolerance is the phenomenon of systemic, antigen specific, immunological hyporesponsiveness that results from oral administration of a protein. The mechanism by which tolerance is generated depends on the amount of antigen administered; low doses favor induction of regulatory T cells while higher doses favor clonal deletion and anergy. The regulatory T cells induced by low doses of oral antigen are triggered by the same antigen to secrete cytokines that suppress, in an antigen nonspecific manner, inflammation in the microenvironment where the triggering antigen is located. This makes possible the targeted delivery of antiinflammatory cytokines to a specific tissue without the requirement for identifying the antigen causing the inflammation. This attribute makes active suppression an attractive mechanism for developing therapies for autoimmune diseases. Orally administered autoantigens have been shown to suppress a wide variety of experimental autoimmune diseases and have recently been applied to the treatment of human autoimmune diseases with promising early results.