Oral tolerance, systemic immunoregulation, and autoimmunity.
Convincing clinical and experimental evidence suggests that the disturbance of important immunoregulatory and suppressive immunological events induced after oral (mucosal) antigen exposure (oral tolerance) may lead to allergic and autoimmune diseases. Within a variety of factors, age of the host and timing of antigen (food) administration are important characteristics in the development of food allergic disease. Induction of tolerance is seen as a Th2 skewed response, which on one side may prevent harmful mucosal immune reactions but on the other side may contribute to adverse responses in the susceptible individual. The primary mechanisms by which tolerance may be mediated include deletion, anergy, suppression, "ignorance," and apoptosis. Cell-mediated delayed hypersensitivity reactions (Th1), which are implicated in the development of autoimmune and gastrointestinal diseases, are particularly well suppressed. Regulatory events after mucosal exposure of antigen are not well characterized and remain controversial. The balance between tolerance (suppression) and sensitization (priming) is dependent on several factors, such as: (a) genetic background, (b) nature and dose of antigen, (c) frequency of administration, (d) age at first antigen exposure, (e) immunological status of the host, (f) antigen transmission via breast milk, and others. Overall there is evidence in rodents that multiple low-dose feeds are more likely to induce regulatory cytokines (e.g., TGF-beta, IL-10, IL-4) in part secreted by CD4+CD25+ T regulatory cells. Despite the powerful suppressive effects of oral autoantigen exposure observed in experimental models of autoimmune diseases (including bystander suppression), their translation into clinical trials of autoimmune diseases has not yet yielded the expected beneficial results.
Strobel
Stephan
S
Immunobiology Unit, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London WC1N 1EH, UK. s.strobel@ich.ucl.ac.uk
D000284:Administration, Oral; D000375:Aging / Q000276:immunology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D008895:Milk, Human / Q000276:immunology
D000941:Antigens