Treatment of disease through oral tolerance

Extract: The immune response to soluble protein antigens differs markedly depending on the route by which that antigen enters the body. In particular, early studies demonstrated that antigens that were first encountered via the gastrointestinal tract (e.g., via oral administration) led to systemic hyporesponsiveness against that antigen. This phenomenon has been termed oral tolerance. Further studies in mouse models of human disease demonstrated the potential for oral tolerance to protect susceptible animals from developing inflammatory and/or autoimmune diseases. This breakthrough finding lead to a surge in interest in oral tolerance as a potential prophylactic/therapeutic agent in human diseases. Here we briefly describe the underlying mechanisms and important factors influencing oral tolerance elucidated through animal models and conclude with a discussion on the translation of these findings to human beings. Numerous studies in mice have demonstrated that the dose of antigen administered is a critical factor influencing oral tolerance. Moreover, two forms of oral tolerance have been delineated which differ in their mechanism of action. High doses of antigen lead to the deletion of antigen-reactive T lymphocytes (T-cells).