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| ORAL TOLERANCE - IMMUNOLOGICAL MECHANISMS AND TREATMENT OF ANIMAL AND HUMAN ORGAN-SPECIFIC AUTOIMMUNE-DISEASES BY ORAL-ADMINISTRATION OF AUTOANTIGENS |
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| Author(s): WEINER HL, FRIEDMAN A, MILLER A, KHOURY SJ, ALSABBAGH A, SANTOS L, SAYEGH M, NUSSENBLATT RB, TRENTHAM DE, HAFLER DA |
| Source: ANNUAL REVIEW OF IMMUNOLOGY Volume: 12 Pages: 809-837 Published: 1994 |
| Times Cited: 748 References: 138 |
| Abstract: Oral tolerance is a long recognized method to induce peripheral immune tolerance. The primary mechanisms by which orally administered antigen induces tolerance are via the generation of active suppression or clonal anergy. Low doses of orally administered antigen favor active suppression whereas higher doses favor clonal anergy. The regulatory cells that mediate active suppression act via the secretion of suppressive cytokines such as TGF beta and IL-4 after being triggered by the oral tolerogen. Furthermore, antigen that stimulates the gut-associated lymphoid tissue preferentially generates a Th2 type response. Because the regulatory cells generated following oral tolerization are triggered in an antigen-specific fashion but suppress in an antigen nonspecific fashion, they mediate ''bystander suppression'' when they encounter the fed autoantigen at the target organ. Thus it may not be necessary to identify the target autoantigen to suppress an organ-specific autoimmune disease via oral tolerance; it is necessary only to administer orally a protein capable of inducing regulatory cells that secrete suppressive cytokines. Orally administered autoantigens suppress several experimental autoimmune models in a disease- and antigen-specific fashion; the diseases include experimental autoimmune encephalomyelitis (EAE), uveitis, and myasthenia, collagen- and adjuvant-induced arthritis, and diabetes in the NOD mouse. In addition, orally administered alloantigen suppresses alloreactivity and prolongs graft survival. Initial clinical trials of oral tolerance in multiple sclerosis, rheumatoid arthritis, and uveitis have demonstrated positive clinical effects with no apparent toxicity and decreases in T cell autoreactivity. |
| Document Type: Review |
| Language: English |
| Reprint Address: WEINER, HL (reprint author), BRIGHAM & WOMENS HOSP, CTR NEUROL DIS, BOSTON, MA 02115 USA |
Addresses:
1. BRIGHAM & WOMENS HOSP, TRANSPLANTAT LAB, BOSTON, MA 02115 USA
2. BETH ISRAEL HOSP, DIV RHEUMATOL, BOSTON, MA 02115 USA
3. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA
4. NEI, IMMUNOL LAB, BETHESDA, MD 20205 USA |
| Publisher: ANNUAL REVIEWS INC, 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 |
| Subject Category: Immunology |
| IDS Number: NF487 |
| ISSN: 0732-0582 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |