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

Abstract

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. © 1997 John Wiley & Sons, Inc. Biopoly 43: 323–335, 1997

Cell stress induced HSP are targets of regulatory T cells: A role for HSP inducing compounds as anti‐inflammatory immuno‐modulators?

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Mucosal Tolerance to Prevent Type 1 Diabetes: Can the Outcome Be Improved in Humans?

“…Mucosal tolerance was discovered early in the 20 th century in models of delayed-type and contact hypersensitivity reactions in guinea pigs, but the mechanisms of tolerance remained ill-defined until the era of modern immunology. The use of cell separation techniques, tests for production of cytokines and transgenic models in which antigen-specific T cells can be tracked in vivo have gradually elucidated mechanisms of mucosal tolerance [3,4]. It has become evident that antigen administration via mucosal routes can result in distinct types of tolerance depending on the route of administration and dose of antigen.…”

Tolerance to Nickel: Oral Nickel Administration Induces a High Frequency of Anergic T Cells with Persistent Suppressor Activity

“…Because the level of peripheral T cell tolerance that can be achieved is known to be dose dependent (27)(28)(29), the more complete and persistent state of tolerance seen after oral NiCl 2 administration might also be explained by the higher dose of tolerogen received via this route.…”