Oral tolerance and the treatment of rheumatoid arthritis.

Abstract

Orally administered antigen encounters the gut-associated lymphoid tissue (GALT) which has the inherent property of not only to protect the host from ingested pathogens but also to prevent the host from reacting to ingested proteins. Thus, orally administered antigens induce systemic hyporesponsiveness to fed proteins and this phenomenon is termed oral tolerance. It was first described in 1911 when Wells fed hen egg proteins to guinea pigs and found them resistant to anaphylaxis when challenged. In 1946, Chase fed guinea pigs the contact-sensitizing agent 2,4-dinitrochlorobenzene (DNCB) and observed that animals had decreased skin reactivity to DNCB. Oral tolerance has also been observed in humans fed and immunized with keytiole limpet hemocyanin (KLH) [45]. There have been many studies trying to elucidate the mechanisms of oral tolerance [74, 113] and now it is clear that oral tolerance is mediated by T cells through different mechanisms depending on the dose of antigen fed. Low-dose antigen favors the induction of regulatory T cells which suppress Thl cell-mediated responses and high-dose antigen induces T cell clonal anergy or deletion (Fig. 1). In recent years, oral tolerance has been used successfully to treat autoimmune diseases in animal models and is now being applied to the treatment of human diseases [113].