当前位置： SCI文献检索 > EUROPEAN JOURNAL OF IMMUNOLOGY期刊下所有文献 > Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse.

Antigen-driven tissue-specific suppression following oral tolerance: orally administered myelin basic protein suppresses proteolipid protein-induced experimental autoimmune encephalomyelitis in the SJL mouse.

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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

al-Sabbagh A,Miller A,Santos LM,Weiner HL

doi

10.1002/eji.1830240926

subject

Has Abstract

pub_date

1994-09-01 00:00:00

pages

2104-9

issue

eissn

0014-2980

issn

1521-4141

journal_volume

pub_type

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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.