ORAL TOLERANCE - ELUCIDATION OF MECHANISMS AND APPLICATION TO TREATMENT OF AUTOIMMUNE-DISEASES

Oral tolerance is the phenomenon of systemic, antigen specific, immuno logical 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 regulator y T cells while higher doses favor clonal deletion and anergy. The reg ulatory T cells induced by low doses of oral antigen are triggered by the same antigen to secrete cytokines that suppress, in an antigen non specific manner, inflammation in the microenvironment where the trigge ring antigen is located. This makes possible the targeted delivery of antiinflammatory cytokines to a specific tissue without the requiremen t for identifying the antigen causing the inflammation. This attribute makes active suppression an attractive mechanism Sor developing thera pies for autoimmune diseases. Orally administered autoantigens have be en shown to suppress a wide variety of experimental autoimmune disease s and have recently been applied to the treatment of human autoimmune diseases with promising early results. (C) 1997 John Wiley & Sons, Inc .