Current Issues in the Treatment of Human Diseases by Mucosal Tolerance

Abstract

Abstract: Tolerance has been defined as a lack of response to self but a more appropriate definition of tolerance is “any mechanism by which a potentially injurious immune response is prevented, suppressed, or shifted to a noninjurious class of immune response.” Thus, tolerance is related to productive self‐recognition, rather than blindness of the immune system to its autocomponents. Oral tolerance, in this sense, is of unique immunologic importance, as it is a continuous natural immunologic event driven by exogenous antigen. Because of their privileged access to the internal milieu, antigens that are continuously in contact with the mucosa are a frontier between foreign and self‐components. Thus, oral tolerance is an immunological mechanism that evolved to treat external agents that gain access to the body via a natural route as internal components that then become part of self. Given this, it would seem logical that autoimmune diseases caused by an inappropriate response to self‐antigens might ultimately be treated by presenting such autoantigens to the mucosal surface where they can be dealt with in a noninjurous (noninflammatory) immunologic environment. Furthermore, mucosal tolerance as a treatment for autoimmune diseases is an attractive concept, as antigen‐specific therapy is the most physiologic means to manipulate immune responses, and mucosal antigen is nontoxic and can be given on a chronic basis. The efficacy of mucosal tolerance has been clearly demonstrated in several animal models.