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Oral tolerance
Ana M C Faria1, Howard L Weiner
1Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Immunological Reviews
|July 29, 2005
Summary
Oral antigen administration induces immune tolerance through various mechanisms, showing promise in animal models and some human trials for autoimmune and inflammatory diseases. Optimizing factors like dose and formulation is key for successful clinical application.
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Oral antigen administration induces immune tolerance via distinct mechanisms, dose-dependently promoting active suppression or clonal anergy/deletion.
- This process involves the induction of specific T-cell subsets, including T-helper 2 (IL-4/IL-10) and Th3 (TGF-beta) cells, alongside regulatory T cells (CD4+CD25+) and latency-associated peptide+ T cells.
Purpose of the Study:
- To review the mechanisms and therapeutic potential of oral tolerance in autoimmune and inflammatory diseases.
- To evaluate the efficacy of oral tolerance in preclinical animal models and human clinical trials.
Main Methods:
- Induction of oral tolerance by antigen administration.
- Assessment of immune responses, including T-cell subsets and cytokine profiles.
- Evaluation in various animal models of autoimmune and non-autoimmune diseases.
- Analysis of human clinical trial data for autoimmune diseases and allergies.
Main Results:
- Oral tolerance effectively suppressed numerous animal models of autoimmune diseases (e.g., EAE, arthritis, diabetes) and non-autoimmune conditions (e.g., asthma, atherosclerosis, Alzheimer's models).
- Human trials for autoimmune diseases (MS, RA) and allergies showed mixed results, with some positive Phase II findings but lack of efficacy in Phase III trials, often confounded by placebo effects.
- Emerging positive results with oral insulin in delaying diabetes onset in at-risk populations indicate potential.
Conclusions:
- Mucosal tolerance, particularly oral administration, offers a non-toxic, antigen-specific approach for treating immune-mediated diseases.
- Successful translation to human therapy requires careful optimization of dose, formulation, route, immune monitoring, and potentially combination strategies.