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Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse.
Eur J Immunol. 1994 Sep; 24(9):2104-9.EJ

Abstract

Immunomodulatory treatment paradigms have been applied to animal models of T cell-mediated autoimmune diseases in an attempt to develop an immunospecific and non-toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self-protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor-beta after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)-induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell-mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue.

Authors+Show Affiliations

Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7522160

Citation

al-Sabbagh, A, et al. "Antigen-driven Tissue-specific Suppression Following Oral Tolerance: Orally Administered Myelin Basic Protein Suppresses Proteolipid Protein-induced Experimental Autoimmune Encephalomyelitis in the SJL Mouse." European Journal of Immunology, vol. 24, no. 9, 1994, pp. 2104-9.
al-Sabbagh A, Miller A, Santos LM, et al. Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse. Eur J Immunol. 1994;24(9):2104-9.
al-Sabbagh, A., Miller, A., Santos, L. M., & Weiner, H. L. (1994). Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse. European Journal of Immunology, 24(9), 2104-9.
al-Sabbagh A, et al. Antigen-driven Tissue-specific Suppression Following Oral Tolerance: Orally Administered Myelin Basic Protein Suppresses Proteolipid Protein-induced Experimental Autoimmune Encephalomyelitis in the SJL Mouse. Eur J Immunol. 1994;24(9):2104-9. PubMed PMID: 7522160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse. AU - al-Sabbagh,A, AU - Miller,A, AU - Santos,L M, AU - Weiner,H L, PY - 1994/9/1/pubmed PY - 1994/9/1/medline PY - 1994/9/1/entrez SP - 2104 EP - 9 JF - European journal of immunology JO - Eur. J. Immunol. VL - 24 IS - 9 N2 - Immunomodulatory treatment paradigms have been applied to animal models of T cell-mediated autoimmune diseases in an attempt to develop an immunospecific and non-toxic form of therapy which can be applied to humans. These treatment paradigms are often directed to T cells with a restricted T cell receptor repertoire or that react with dominant peptide determinants. Experimental data, however, suggests that even if the initial T cell response is restricted to a specific self-protein in the target organ, spreading autoimmunity may develop with broadening of T cell autoreactivity to additional epitopes of the same autoantigen or to different autoantigens in the target organ. Thus, multiple autoantigens may become targets of the autoimmune response. This makes immunotherapeutic strategies based on suppressing responses to restricted proteins or clones of cells problematic. We have previously shown that suppression of experimental autoimmune encephalomyelitis (EAE) in the Lewis rat by oral myelin basic protein (MBP) is mediated by the release of transforming growth factor-beta after triggering by the oral tolerogen. Here, we report that in the SJL model of EAE oral administration of an autoantigen from the target tissue suppresses disease independent of whether it is or is not the inciting antigen. Thus, orally administered MBP or MBP peptides suppress proteolipid protein (PLP)-induced EAE, whereas intravenously administered MBP does not. Both oral and intravenous PLP, however, suppressed PLP disease. These findings have important implications for the use of oral tolerance as a therapeutic approach for the treatment of T cell-mediated inflammatory autoimmune diseases in man in which the inciting autoantigen is unknown or in which there is autoreactivity to multiple autoantigens in the target tissue. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/7522160/Antigen_driven_tissue_specific_suppression_following_oral_tolerance:_orally_administered_myelin_basic_protein_suppresses_proteolipid_protein_induced_experimental_autoimmune_encephalomyelitis_in_the_SJL_mouse_ L2 - https://doi.org/10.1002/eji.1830240926 DB - PRIME DP - Unbound Medicine ER -