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PMID: 16048553 Published · ppublish English Journal Article Review

Oral tolerance.

Immunological reviews ·Vol. 206 ·2005-08-00 ·Pages 232-59

Faria AM, Weiner HL

Abstract

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy.

MeSH Terms
Animals Antigens/administration & dosage,immunology Humans Immune Tolerance Immunity, Mucosal Intestinal Mucosa/immunology Mouth Mucosa/immunology
Chemicals
Antigens
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Faria Ana M C
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Weiner Howard L
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Article Info
Journal
Immunological reviews
Abbr.
Immunol Rev
ISSN
0105-2896
DOI
10.1111/j.0105-2896.2005.00280.x
Published
2005-08-00
Pages
232-59
Language
English
Region
England
NLM ID
7702118
PMCID
PMC3076704
Subset
IM
Grants
NIAID NIH HHS · R01 AI043458 · United States
NIAID NIH HHS · R01 AI043458-12 · United States
External Links
PubMed source DOI: 10.1111/j.0105-2896.2005.00280.x PMC Full Text View journal details
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